Is SMARCD1 p.Pro313Ser (c.937C>T) pathogenic?

SMARCD1 p.Pro313Ser (c.937C>T) is classified Uncertain significance in SMARCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-12). AlphaMissense: likely pathogenic (0.6274); Absent from gnomAD v4.1.

How common is SMARCD1 p.Pro313Ser (c.937C>T) in the general population?

SMARCD1 p.Pro313Ser (c.937C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCD1 p.Pro313Ser (c.937C>T)?

AlphaMissense predicts likely pathogenic (score 0.6274) — an in-silico prediction, not a clinical call.

SMARCD1 p.Pro313Ser

c.937C>T · VCV4057059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6274 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6274	likely pathogenic
REVEL	0.33	indeterminate
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 13 kb · p 8.4e-25 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMARCD1
Protein: p.Pro313Ser
Coding: c.937C>T
MANE Select: NM_003076
Type: single nucleotide variant
Location: chr12:50090304 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 12 PDB
Residue 313: the swib/mdm2 domain; an α-helix; the 'interaction with smarcc1 and smarcc2' region; the 'necessary for gr/nr3c1-mediated remodeling and transcription from chromatin; required for gr/nr3c1 interaction with the brg1/smarca4 complex in vivo' region

Full SMARCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCD1 p.Ala302Gly Uncertain significance ★★ same type
SMARCD1 p.Arg334Gln Uncertain significance ★★ ⚠ same type
SMARCD1 p.Asp247Gly Uncertain significance ★★ ⚠ same type
SMARCD1 p.Ile184Val Uncertain significance ★★ ⚠ same type
SMARCD1 p.Ile323Val Uncertain significance ★★ ⚠ same type
SMARCD1 p.Thr189Ser Uncertain significance ★★ ⚠ same type
SMARCD1 p.Thr203Met Uncertain significance ★★ ⚠ same type
SMARCD1 c.1036-4A>G Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/smarcd1-p-pro313ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown