Is SMARCA4 p.Pro230Arg (c.689C>G) pathogenic?

SMARCA4 p.Pro230Arg (c.689C>G) is classified Uncertain significance in SMARCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-06). AlphaMissense: likely benign (0.1648); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Pro230Arg (c.689C>G)?

SMARCA4 p.Pro230Arg (c.689C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Pro230Arg (c.689C>G) in the general population?

SMARCA4 p.Pro230Arg (c.689C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA4 p.Pro230Arg (c.689C>G)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

SMARCA4 p.Pro230Arg

c.689C>G · rs2145783429 · VCV1756028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -11.97	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,911 bp · p 0.24 · regional, not allelic
Overall
CADD	21.5	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

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: SMARCA4
Protein: p.Pro230Arg
Coding: c.689C>G
MANE Select: NM_003072
dbSNP: rs2145783429
Type: single nucleotide variant
Location: chr19:10986522 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 230: the 'necessary for interaction with ss18l1/crest' region; the 'disordered' region

Full SMARCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SMARCA4 p.Pro230Ala Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Pro230Ser Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Pro230= Likely benign ★★ same residue
SMARCA4 p.Pro230Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCA4 c.1943+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.2438+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCA4 c.3216-1G>C Likely pathogenic ★★ same condition
SMARCA4 c.3546+1G>A Likely pathogenic ★★ 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/smarca4-p-pro230arg (accessed [today's date]).

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