Is BCAR3 p.Arg158Cys (c.472C>T) pathogenic?

BCAR3 p.Arg158Cys (c.472C>T) is classified Uncertain significance in BCAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.0914); Ultra-rare (popmax 0.0245%, eas).

How common is BCAR3 p.Arg158Cys (c.472C>T) in the general population?

BCAR3 p.Arg158Cys (c.472C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about BCAR3 p.Arg158Cys (c.472C>T)?

AlphaMissense predicts likely benign (score 0.0914) — an in-silico prediction, not a clinical call.

BCAR3 p.Arg158Cys

c.472C>T · rs374784683 · VCV2403069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0914 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0914	likely benign
REVEL	0.6	indeterminate
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 113 kb · p 0.0058 · regional, not allelic
Overall
CADD	27.2	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 0.0245% East Asian · 11/44,840 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00347% 56/1,613,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,076
Remaining individualsnot grpmax-eligible	0.008%	12,499
South Asian	0.00659%	15,180
Admixed American	0.00333%	29,997
European (non-Finnish)	0.00263%	38,065
African / African-American	0.00133%	74,978

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: BCAR3
Protein: p.Arg158Cys
Coding: c.472C>T
MANE Select: NM_003567
dbSNP: rs374784683
Type: single nucleotide variant
Location: chr1:93592279 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.36 · 1 PDB
Residue 158: the sh2 domain

Full BCAR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAR3 p.Arg758Gln Uncertain significance ★★ ⚠ same type
BCAR3 p.Asn733Ser Benign ★★ same type
BCAR3 p.Thr506= Benign ★★ same type
BCAR3 p.Ala196Ser Uncertain significance ★ ⚠ same type
BCAR3 p.Ala196Thr Uncertain significance ★ ⚠ same type
BCAR3 p.Ala211Asp Uncertain significance ★ ⚠ same type
BCAR3 p.Ala247Thr Uncertain significance ★ ⚠ same type
BCAR3 p.Ala391Val 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/bcar3-p-arg158cys (accessed [today's date]).

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