# NM_014314.4(RIGI):c.2730C>T (p.Asp910=)

https://sugi.bio/variant/rigi-p-asp910

## Summary

**RIGI p.Asp910= (c.2730C>T)** is classified **Likely benign** in RIGI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). Absent from gnomAD v4.1.

**At a glance:** Likely benign · review: Single submitter · 1 submitter · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the RIGI gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [RIGI](https://sugi.bio/atlas/gene/RIGI/) |
| Protein change (HGVS p.) | p.Asp910= |
| Coding change (HGVS c.) | c.2730C>T |
| MANE Select transcript | [NM_014314](https://www.ncbi.nlm.nih.gov/nuccore/NM_014314) |
| Variant type | single nucleotide variant |
| Location | chr9:32457170-32457170 (GRCh38) |
| ClinVar | [VCV3649869](https://www.ncbi.nlm.nih.gov/clinvar/variation/3649869/) |

**All HGVS expressions:** `NC_000009.11:g.32457168G>A`, `NC_000009.12:g.32457170G>A`, `NG_046918.1:g.74155C>T`, `NM_001385907.1:c.2724C>T`, `NM_001385909.1:c.2559C>T`, `NM_001385910.1:c.2289C>T`, `NM_001385912.1:c.2121C>T`, `NM_001385913.1:c.2715C>T`, `NM_001385914.1:c.2286C>T`, `NM_014314.4:c.2730C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 0.387, GERP -3.92, phastCons 0.979 — weakly conserved position
- CADD: **PHRED 4.457**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Protein context {#protein}

Residue **910** lies in an α-helix; the rlr ctr domain; the 'interaction with zc3hav1' region; the 'mediates interaction with rnf135' region.

AlphaFold model confidence (whole protein): pLDDT 85.40, 52% of residues very-high.

**44 experimental structure(s)** (PDB): [2LWD](https://www.rcsb.org/structure/2LWD), [2LWE](https://www.rcsb.org/structure/2LWE), [2QFB](https://www.rcsb.org/structure/2QFB), [2QFD](https://www.rcsb.org/structure/2QFD), [2RMJ](https://www.rcsb.org/structure/2RMJ), [2YKG](https://www.rcsb.org/structure/2YKG) — incl. mutant structure 2LWE.

## What this gene does {#gene-function}

*Describes the biological roles of RIGI (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** RIGI's established molecular role includes RNA helicase activity. p.Asp910= falls in the rlr ctr domain. In Reactome, RIGI is annotated in disease pathway(s) including **Evasion by RSV of host interferon responses**, **RSV-host interactions**.

**Disease mechanism (Reactome):** RIGI loss or alteration is curated in [Evasion by RSV of host interferon responses](https://reactome.org/content/detail/R-HSA-9833109), [RSV-host interactions](https://reactome.org/content/detail/R-HSA-9833110), [SARS-CoV-1 activates/modulates innate immune responses](https://reactome.org/content/detail/R-HSA-9692916).

### Pathways affected {#pathways}

RIGI participates in **15 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Evasion by RSV of host interferon responses](https://reactome.org/content/detail/R-HSA-9833109) | curated |
| ⚕ [RSV-host interactions](https://reactome.org/content/detail/R-HSA-9833110) | curated |
| ⚕ [SARS-CoV-1 activates/modulates innate immune responses](https://reactome.org/content/detail/R-HSA-9692916) | curated |
| ⚕ [SARS-CoV-2 activates/modulates innate and adaptive immune responses](https://reactome.org/content/detail/R-HSA-9705671) | curated |
| [DDX58/IFIH1-mediated induction of interferon-alpha/beta](https://reactome.org/content/detail/R-HSA-168928) | curated |
| [ISG15 antiviral mechanism](https://reactome.org/content/detail/R-HSA-1169408) | curated |
| [Modulation of host responses by IFN-stimulated genes](https://reactome.org/content/detail/R-HSA-9909505) | curated |
| [NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10](https://reactome.org/content/detail/R-HSA-933543) | curated |
| [OAS antiviral response](https://reactome.org/content/detail/R-HSA-8983711) | curated |
| [Ovarian tumor domain proteases](https://reactome.org/content/detail/R-HSA-5689896) | curated |
| [TRAF3-dependent IRF activation pathway](https://reactome.org/content/detail/R-HSA-918233) | curated |
| [TRAF6 mediated IRF7 activation](https://reactome.org/content/detail/R-HSA-933541) | curated |
| [Ub-specific processing proteases](https://reactome.org/content/detail/R-HSA-5689880) | curated |
| [Negative regulators of DDX58/IFIH1 signaling](https://reactome.org/content/detail/R-HSA-936440) | electronic |
| [TRAF6 mediated NF-kB activation](https://reactome.org/content/detail/R-HSA-933542) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA helicase activity, double-stranded RNA binding, single-stranded RNA binding, GTP binding, zinc ion binding, ATP hydrolysis activity.

**Biological process:** positive regulation of defense response to virus by host, cytoplasmic pattern recognition receptor signaling pathway, detection of virus, positive regulation of gene expression, regulation of cell migration, positive regulation of granulocyte macrophage colony-stimulating factor production.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-04-20.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2024-04-20 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related RIGI variant pages (same residue, condition, or type): [RIGI p.Asp910Glu](/variant/rigi-p-asp910glu), [RIGI p.Asp910Tyr](/variant/rigi-p-asp910tyr), [RIGI c.1923+1G>A](/variant/rigi-c-1923-plus-1g-a), [RIGI c.954-6T>G](/variant/rigi-c-954-minus-6t-g), [RIGI p.Ala436Val](/variant/rigi-p-ala436val), [RIGI p.Ala486Thr](/variant/rigi-p-ala486thr), [RIGI p.Ala537Ser](/variant/rigi-p-ala537ser), [RIGI p.Ala537Thr](/variant/rigi-p-ala537thr).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3649869). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*