Is BCAR3 p.Ala490Val (c.1469C>T) pathogenic?

BCAR3 p.Ala490Val (c.1469C>T) is classified Uncertain significance in BCAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0716); Ultra-rare (popmax 0.0493%, mid).

How common is BCAR3 p.Ala490Val (c.1469C>T) in the general population?

BCAR3 p.Ala490Val (c.1469C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about BCAR3 p.Ala490Val (c.1469C>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

BCAR3 p.Ala490Val

c.1469C>T · rs776226561 · VCV2212815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.96	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 0.28	GERP -3.9
Regional constraint	o/e 0.92	unconstrained · MANE · 113 kb · p 0.0058 · regional, not allelic
Overall
CADD	1.96	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00316% 51/1,613,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
East Asian	0.00892%	11,217
European (non-Finnish)	0.00339%	29,499
Admixed American	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,858
South Asian	0.0011%	91,076

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.Ala490Val
Coding: c.1469C>T
MANE Select: NM_003567
dbSNP: rs776226561
Type: single nucleotide variant
Location: chr1:93582518 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.36 · 1 PDB

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-ala490val (accessed [today's date]).

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