Is SMARCA2 p.Ala681Pro (c.2041G>C) pathogenic?

SMARCA2 p.Ala681Pro (c.2041G>C) is classified Uncertain significance in SMARCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). AlphaMissense: likely pathogenic (0.9852); No allele count reported in gnomAD v4.1 (AN 1,613,470).

How common is SMARCA2 p.Ala681Pro (c.2041G>C) in the general population?

SMARCA2 p.Ala681Pro (c.2041G>C) is no allele count reported in gnomAD v4.1 (AN 1,613,470) (gnomAD).

What do computational predictors say about SMARCA2 p.Ala681Pro (c.2041G>C)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

SMARCA2 p.Ala681Pro

c.2041G>C · VCV4689809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,470)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic
REVEL	0.578	indeterminate
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.75	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 8,630 bp · p 3.8e-08 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,470). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SMARCA2
Protein: p.Ala681Pro
Coding: c.2041G>C
MANE Select: NM_003070
Type: single nucleotide variant
Location: chr9:2077633 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB

Full SMARCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCA2 p.Ala1138Pro Pathogenic/Likely pathogenic ★★ same type
SMARCA2 p.Ala1160Gly Pathogenic ★★ same type
SMARCA2 p.Ala1201Glu Pathogenic/Likely pathogenic ★★ same type
SMARCA2 p.Ala1201Val Pathogenic/Likely pathogenic ★★ same type
SMARCA2 p.Arg1105Cys Pathogenic ★★ same type
SMARCA2 p.Arg1105His Pathogenic ★★ same type
SMARCA2 p.Arg1105Pro Pathogenic/Likely pathogenic ★★ same type
SMARCA2 p.Arg1159Gln Pathogenic/Likely pathogenic ★★ 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/smarca2-p-ala681pro (accessed [today's date]).

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