Is SMARCA2 p.Pro167Arg (c.500C>G) pathogenic?

SMARCA2 p.Pro167Arg (c.500C>G) is classified Uncertain significance in SMARCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.3152); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Pro167Arg (c.500C>G)?

SMARCA2 p.Pro167Arg (c.500C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCA2 p.Pro167Arg (c.500C>G) in the general population?

SMARCA2 p.Pro167Arg (c.500C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA2 p.Pro167Arg (c.500C>G)?

AlphaMissense predicts likely benign (score 0.3152) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro167Arg

c.500C>G · rs376294726 · VCV2307437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3152 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3152	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.5, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.08 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: SMARCA2
Protein: p.Pro167Arg
Coding: c.500C>G
MANE Select: NM_003070
dbSNP: rs376294726
Type: single nucleotide variant
Location: chr9:2039610 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 167: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SMARCA2 p.Ala1138Pro Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg505Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SMARCA2 p.Ala1215Val Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Ala1389Ser Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Arg1266Gly Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Arg427Cys Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Glu1509Asp Uncertain significance ★★ ⚠ same condition
SMARCA2 p.Gly304Trp Uncertain significance ★★ same condition

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-pro167arg (accessed [today's date]).

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