Is SMARCA2 p.Pro244Leu (c.731C>T) pathogenic?

SMARCA2 p.Pro244Leu (c.731C>T) is classified Likely benign in SMARCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-19). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Pro244Leu (c.731C>T)?

SMARCA2 p.Pro244Leu (c.731C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCA2 p.Pro244Leu (c.731C>T) in the general population?

SMARCA2 p.Pro244Leu (c.731C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about SMARCA2 p.Pro244Leu (c.731C>T)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro244Leu

c.731C>T · rs562886418 · VCV2389574

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP -3.4
Regional constraint	o/e 1.18	unconstrained · MANE · 7,571 bp · p 0.073 · regional, not allelic
Overall
CADD	16.32	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

Grpmax group 0.0187% African / African-American · 14/74,848 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00977%

Overall 0.00372% 60/1,612,486 alleles · ultra-rare exomes 54/1,460,440 · genomes 6/152,046 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,346
South Asian	0.0187%	5,348
Finnishnot grpmax-eligible	0.011%	9,091
Remaining individualsnot grpmax-eligible	0.00481%	20,808
European (non-Finnish)	0.00161%	62,071

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: SMARCA2
Protein: p.Pro244Leu
Coding: c.731C>T
MANE Select: NM_003070
dbSNP: rs562886418
Type: single nucleotide variant
Location: chr9:2039841 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 244: 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.Pro244= Likely benign ★ same residue
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

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-pro244leu (accessed [today's date]).

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