Is BCLAF1 p.Ile232Val (c.694A>G) pathogenic?

BCLAF1 p.Ile232Val (c.694A>G) is classified Uncertain significance in BCLAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0535); Ultra-rare (popmax 0.0534%, afr).

How common is BCLAF1 p.Ile232Val (c.694A>G) in the general population?

BCLAF1 p.Ile232Val (c.694A>G) is ultra-rare (popmax 0.0534%, afr) (gnomAD).

What do computational predictors say about BCLAF1 p.Ile232Val (c.694A>G)?

AlphaMissense predicts likely benign (score 0.0535) — an in-silico prediction, not a clinical call.

BCLAF1 p.Ile232Val

c.694A>G · rs140163198 · VCV3133516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0535 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0535	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.33	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 4.1	GERP 1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 223 bp · p 0.0066 · regional, not allelic
Overall
CADD	20.8	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

Grpmax group 0.0534% African / African-American · 40/74,938 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00744% 120/1,613,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0534%	1,873
European (non-Finnish)	0.00653%	15,323
Remaining individualsnot grpmax-eligible	0.0048%	20,825

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: BCLAF1
Protein: p.Ile232Val
Coding: c.694A>G
MANE Select: NM_014739
dbSNP: rs140163198
Type: single nucleotide variant
Location: chr6:136278187 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 47.04 · 2 PDB
Residue 232: the 'disordered' region

Full BCLAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCLAF1 p.Ile232Thr Uncertain significance ★ ⚠ same residue
BCLAF1 p.Gly210Ser Benign/Likely benign ★★ same type
BCLAF1 c.2397+1G>C Uncertain significance ★ same type
BCLAF1 p.Ala169Thr Uncertain significance ★ ⚠ same type
BCLAF1 p.Ala310Val Uncertain significance ★ ⚠ same type
BCLAF1 p.Ala669Val Uncertain significance ★ ⚠ same type
BCLAF1 p.Arg107Gln Uncertain significance ★ ⚠ same type
BCLAF1 p.Arg111His Uncertain significance ★ ⚠ 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/bclaf1-p-ile232val (accessed [today's date]).

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