Is SMARCA5 p.Pro229Arg (c.686C>G) pathogenic?

SMARCA5 p.Pro229Arg (c.686C>G) is classified Uncertain significance in SMARCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). AlphaMissense: likely benign (0.2957); Absent from gnomAD v4.1.

How common is SMARCA5 p.Pro229Arg (c.686C>G) in the general population?

SMARCA5 p.Pro229Arg (c.686C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA5 p.Pro229Arg (c.686C>G)?

AlphaMissense predicts likely benign (score 0.2957) — an in-silico prediction, not a clinical call.

SMARCA5 p.Pro229Arg

c.686C>G · VCV4880975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2957	likely benign
REVEL	0.504	indeterminate
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 7,184 bp · p 1.1e-25 · regional, not allelic
Overall
CADD	25.0	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: SMARCA5
Protein: p.Pro229Arg
Coding: c.686C>G
MANE Select: NM_003601
Type: single nucleotide variant
Location: chr4:143526345 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.41 · 15 PDB
Residue 229: the helicase atp-binding domain

Full SMARCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCA5 p.Glu893Lys Pathogenic ★★ same type
SMARCA5 p.Pro339Ser Likely pathogenic ★★ same type
SMARCA5 p.Lys694Glu Uncertain significance ★★ ⚠ same type
SMARCA5 p.Met386Thr Uncertain significance ★★ ⚠ same type
SMARCA5 p.Ala51= Likely benign ★★ same type
SMARCA5 p.Phe92= Benign ★★ same type
SMARCA5 p.Ser26= Benign/Likely benign ★★ same type
SMARCA5 c.2283+1G>A 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/smarca5-p-pro229arg (accessed [today's date]).

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