Is SMARCC2 p.His331Arg (c.992A>G) pathogenic?

SMARCC2 p.His331Arg (c.992A>G) is classified Uncertain significance in SMARCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-17). AlphaMissense: ambiguous (0.4815); Absent from gnomAD v4.1.

How common is SMARCC2 p.His331Arg (c.992A>G) in the general population?

SMARCC2 p.His331Arg (c.992A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCC2 p.His331Arg (c.992A>G)?

AlphaMissense predicts ambiguous (score 0.4815) — an in-silico prediction, not a clinical call.

SMARCC2 p.His331Arg

c.992A>G · rs2135731469 · VCV1310717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4815 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4815	ambiguous
REVEL	0.21	benign-leaning
SaProt	LLR -4.38	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 3,062 bp · p 0.22 · regional, not allelic
Overall
CADD	23.3	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

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: SMARCC2
Protein: p.His331Arg
Coding: c.992A>G
MANE Select: NM_001330288
dbSNP: rs2135731469
Type: single nucleotide variant
Location: chr12:56181066 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 9 PDB
Residue 331: a UniProt-annotated variant site (in css8); the 'disordered' region

Full SMARCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCC2 c.1311-3C>G Pathogenic/Likely pathogenic ★★ same type
SMARCC2 c.1926+1G>A Pathogenic/Likely pathogenic ★★ same type
SMARCC2 c.1926+1G>T Pathogenic/Likely pathogenic ★★ same type
SMARCC2 c.1926+2T>C Pathogenic/Likely pathogenic ★★ same type
SMARCC2 p.Arg116His Likely pathogenic ★★ same type
SMARCC2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
SMARCC2 p.Arg269Ter Pathogenic/Likely pathogenic ★★ same type
SMARCC2 p.Arg474Ter 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/smarcc2-p-his331arg (accessed [today's date]).

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