Is SMARCA2 p.Ile77= (c.231C>T) pathogenic?

SMARCA2 p.Ile77= (c.231C>T) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.936%, amr); Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Ile77= (c.231C>T)?

SMARCA2 p.Ile77= (c.231C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCA2 p.Ile77= (c.231C>T) in the general population?

SMARCA2 p.Ile77= (c.231C>T) is rare (popmax 0.936%, amr) (gnomAD).

SMARCA2 p.Ile77=

c.231C>T · rs148086416 · VCV588510

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.936%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -5.4
Overall
CADD	1.712	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.936% Admixed American · 561/59,966 alleles

Filtering AF 0.872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.846%

Overall 0.0422% 681/1,613,496 alleles · rare exomes 590/1,461,252 · genomes 91/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.936%	107
East Asian	0.0736%	1,360
African / African-American	0.0333%	2,999
Remaining individualsnot grpmax-eligible	0.032%	3,124
European (non-Finnish)	0.00348%	28,771
South Asian	0.0011%	91,016

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: SMARCA2
Protein: p.Ile77=
Coding: c.231C>T
MANE Select: NM_003070
dbSNP: rs148086416
Type: single nucleotide variant
Location: chr9:2032957 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB

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.Ile77Val Uncertain significance ★ ⚠ 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-ile77 (accessed [today's date]).

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