Is SMARCC2 p.Ser102Arg (c.306T>A) pathogenic?

SMARCC2 p.Ser102Arg (c.306T>A) is classified Uncertain significance in SMARCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1.

How common is SMARCC2 p.Ser102Arg (c.306T>A) in the general population?

SMARCC2 p.Ser102Arg (c.306T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCC2 p.Ser102Arg (c.306T>A)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

SMARCC2 p.Ser102Arg

c.306T>A · VCV3770069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 9% in SMARCC2
REVEL	0.189	benign-leaning
SaProt	LLR -12.60	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 1,255 bp · p 9.2e-08 · regional, not allelic
Overall
CADD	22.8	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.Ser102Arg
Coding: c.306T>A
MANE Select: NM_001330288
Type: single nucleotide variant
Location: chr12:56186166 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 9 PDB
Residue 102: the marr-like domain; the 'marr-like, brct and chromo domains module' 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-ser102arg (accessed [today's date]).

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