# NM_001098426.2(SMARCD2):c.1314C>T (p.Val438=)

https://sugi.bio/variant/smarcd2-p-val438

## Summary

**SMARCD2 p.Val438= (c.1314C>T)** is classified **Likely benign** in SMARCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-26). 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 SMARCD2 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 | [SMARCD2](https://sugi.bio/atlas/gene/SMARCD2/) |
| Protein change (HGVS p.) | p.Val438= |
| Coding change (HGVS c.) | c.1314C>T |
| MANE Select transcript | [NM_001098426](https://www.ncbi.nlm.nih.gov/nuccore/NM_001098426) |
| Variant type | single nucleotide variant |
| Location | chr17:63833590-63833590 (GRCh38) |
| ClinVar | [VCV3687002](https://www.ncbi.nlm.nih.gov/clinvar/variation/3687002/) |

**All HGVS expressions:** `NC_000017.10:g.61910950G>A`, `NC_000017.11:g.63833590G>A`, `NG_053004.1:g.14402C>T`, `NM_001098426.2:c.1314C>T`, `NM_001330439.1:c.1089C>T`, `NM_001330440.2:c.1170C>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 1.869, GERP 1.28, phastCons 1 — weakly conserved position
- CADD: **PHRED 8.248**. 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: **below the reporting threshold**. This position is scored for a different substitution (G>T, Δ0.23 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- 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.*

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

**SMARCD2** population constraint: LOEUF 0.762, pLI 2.6057e-07, missense-Z 1.89. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 78.38, 58% of residues very-high.

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

*Describes the biological roles of SMARCD2 (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.*


### Pathways affected {#pathways}

SMARCD2 participates in **10 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)](https://reactome.org/content/detail/R-HSA-9934037) | curated |
| [Formation of the embryonic stem cell BAF (esBAF) complex](https://reactome.org/content/detail/R-HSA-9933946) | curated |
| [Formation of the non-canonical BAF (ncBAF) complex](https://reactome.org/content/detail/R-HSA-9933947) | curated |
| [Formation of the polybromo-BAF (pBAF) complex](https://reactome.org/content/detail/R-HSA-9933939) | curated |
| [RMTs methylate histone arginines](https://reactome.org/content/detail/R-HSA-3214858) | curated |
| [RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known](https://reactome.org/content/detail/R-HSA-8939243) | curated |
| [SWI/SNF chromatin remodelers](https://reactome.org/content/detail/R-HSA-9932451) | curated |
| [Regulation of MITF-M-dependent genes involved in pigmentation](https://reactome.org/content/detail/R-HSA-9824585) | electronic |
| [Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)](https://reactome.org/content/detail/R-HSA-9845323) | electronic |
| [Somatic hypermutation of immunoglobulin genes](https://reactome.org/content/detail/R-HSA-9938024) | electronic |

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

**Biological process:** nucleosome disassembly, chromatin remodeling.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-12-26.

**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 | 2024-12-26 |

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

## Similar variants {#similar}

Related SMARCD2 variant pages (same residue, condition, or type): [SMARCD2 p.Arg192Ter](/variant/smarcd2-p-arg192ter), [SMARCD2 c.922-3C>T](/variant/smarcd2-c-922-minus-3c-t), [SMARCD2 p.Ala434Thr](/variant/smarcd2-p-ala434thr), [SMARCD2 p.Ala6Val](/variant/smarcd2-p-ala6val), [SMARCD2 p.Arg118Cys](/variant/smarcd2-p-arg118cys), [SMARCD2 p.Arg148Gln](/variant/smarcd2-p-arg148gln), [SMARCD2 p.Arg150Trp](/variant/smarcd2-p-arg150trp), [SMARCD2 p.Arg175His](/variant/smarcd2-p-arg175his).

### 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 3687002). 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.*