# NM_014026.6(DCPS):c.906C>T (p.Ile302=)

https://sugi.bio/variant/dcps-p-ile302

## Summary

**DCPS p.Ile302= (c.906C>T)** is classified **Benign/Likely benign** in DCPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Rare (popmax 0.111%, eas).

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs148207687 · 2 submitters · rare (popmax 0.111%, eas)

## For patients & families {#patients}

This is a change in the DCPS gene that is classified as benign/likely benign — not considered disease-causing, submitted by 2 submitters.

*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 | [DCPS](https://sugi.bio/atlas/gene/DCPS/) |
| Protein change (HGVS p.) | p.Ile302= |
| Coding change (HGVS c.) | c.906C>T |
| MANE Select transcript | [NM_014026](https://www.ncbi.nlm.nih.gov/nuccore/NM_014026) |
| dbSNP | [rs148207687](https://www.ncbi.nlm.nih.gov/snp/rs148207687/) |
| Variant type | single nucleotide variant |
| Location | chr11:126345505-126345505 (GRCh38) |
| ClinVar | [VCV733666](https://www.ncbi.nlm.nih.gov/clinvar/variation/733666/) |

**All HGVS expressions:** `NC_000011.10:g.126345505C>T`, `NC_000011.9:g.126215400C>T`, `NG_053153.1:g.47205C>T`, `NM_001350236.2:c.927C>T`, `NM_014026.6:c.906C>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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor gain** (Δ 0.29) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -5.467, GERP 0.595 — fast-evolving / accelerated position
- CADD: **PHRED 7.011**. 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 deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.29**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.29**.
- Pangolin: Δ**0.23** (gain), gain 0.23 / loss 0.00. Agrees with SpliceAI. An independent predictor to SpliceAI — a different model trained on different data. *Descriptive; ClinGen's SVI calibration covers SpliceAI, not Pangolin, so no ACMG code is assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.111%** (eas) · FAF95 0.0963% · FAF99 0.0943% · 50/44,882 in the highest group · 1,351/1,614,096 alleles overall — rare (popmax 0.111%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.111% | 898 |
| European (non-Finnish) | 0.101% | 989 |
| Remaining individuals (not grpmax-eligible) | 0.0768% | 1,302 |
| Middle Eastern | 0.0495% | 2,021 |
| African / African-American | 0.0267% | 3,752 |
| Admixed American | 0.0233% | 4,287 |
| Finnish (not grpmax-eligible) | 0.0219% | 4,567 |
| South Asian | 0.00988% | 10,121 |

*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.*

## Gene constraint & dosage {#gene-context}

**DCPS** population constraint: LOEUF 1, pLI 2.2711e-07, missense-Z -0.11585. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **302** lies in an α-helix.

AlphaFold model confidence (whole protein): pLDDT 89.18, 79% of residues very-high.

**11 experimental structure(s)** (PDB): [1ST0](https://www.rcsb.org/structure/1ST0), [1ST4](https://www.rcsb.org/structure/1ST4), [1XML](https://www.rcsb.org/structure/1XML), [1XMM](https://www.rcsb.org/structure/1XMM), [3BL7](https://www.rcsb.org/structure/3BL7), [3BL9](https://www.rcsb.org/structure/3BL9).

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

*Describes the biological roles of DCPS (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:** DCPS's established molecular role includes RNA 7-methylguanosine cap binding.


### Pathways affected {#pathways}

DCPS participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [mRNA decay by 3' to 5' exoribonuclease](https://reactome.org/content/detail/R-HSA-429958) | curated |

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

**Molecular function:** RNA 7-methylguanosine cap binding, identical protein binding, 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity.

**Biological process:** mRNA cis splicing, via spliceosome, mRNA methylguanosine-cap decapping.

## Clinical significance {#significance}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-10-01.

**Submitter consensus:** conflicting (1 Benign, 1 Likely benign).

**Submission history:** 2 submissions (2019–2025); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2019-12-31 |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2025-10-01 |

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

## Similar variants {#similar}

Related DCPS variant pages (same residue, condition, or type): [DCPS p.Arg152Ter](/variant/dcps-p-arg152ter), [DCPS p.Ala184Thr](/variant/dcps-p-ala184thr), [DCPS p.Arg145Cys](/variant/dcps-p-arg145cys), [DCPS p.Arg242Gly](/variant/dcps-p-arg242gly), [DCPS p.Pro235Leu](/variant/dcps-p-pro235leu), [DCPS p.Ala186=](/variant/dcps-p-ala186), [DCPS p.Ala80=](/variant/dcps-p-ala80), [DCPS p.Asp324=](/variant/dcps-p-asp324).

### 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 733666). 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.*