Is SMARCA4 p.Pro230= (c.690C>T) pathogenic?

SMARCA4 p.Pro230= (c.690C>T) is classified Likely benign in SMARCA4 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Very rare (popmax 0.00471%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Pro230= (c.690C>T)?

SMARCA4 p.Pro230= (c.690C>T) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Pro230= (c.690C>T) in the general population?

SMARCA4 p.Pro230= (c.690C>T) is very rare (popmax 0.00471%, nfe) (gnomAD).

SMARCA4 p.Pro230=

c.690C>T · rs372941839 · VCV238511

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00471%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -3.4
Overall
CADD	0.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00471% European (non-Finnish) · 54/1,146,696 alleles

Filtering AF 0.00369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0033%

Overall 0.00389% 60/1,543,408 alleles · very rare exomes 51/1,391,208 · genomes 9/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00471%	21,235
African / African-American	0.00411%	24,344
Remaining individualsnot grpmax-eligible	0.00333%	30,015
South Asian	0.00119%	84,016

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SMARCA4
Protein: p.Pro230=
Coding: c.690C>T
MANE Select: NM_003072
dbSNP: rs372941839
Type: single nucleotide variant
Location: chr19:10986523 (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

Also linked: rhabdoid tumor predisposition syndrome 2

Similar variants

SMARCA4 p.Pro230Ala Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Pro230Ser Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Pro230Arg Uncertain significance ★ ⚠ same residue
SMARCA4 p.Pro230Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCA4 c.1943+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.2274+1G>T Likely pathogenic ★★ same condition
SMARCA4 c.2438+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCA4 c.3216-1G>C 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-pro230 (accessed [today's date]).

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