Is BCAR3 p.Phe504Ser (c.1511T>C) pathogenic?

BCAR3 p.Phe504Ser (c.1511T>C) is classified Uncertain significance in BCAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: ambiguous (0.4287); Very rare (popmax 0.00441%, nfe).

How common is BCAR3 p.Phe504Ser (c.1511T>C) in the general population?

BCAR3 p.Phe504Ser (c.1511T>C) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about BCAR3 p.Phe504Ser (c.1511T>C)?

AlphaMissense predicts ambiguous (score 0.4287) — an in-silico prediction, not a clinical call.

BCAR3 p.Phe504Ser

c.1511T>C · rs769691162 · VCV2229636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4287	ambiguous
REVEL	0.424	indeterminate
SaProt	LLR -1.73	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 113 kb · p 0.0058 · regional, not allelic
Overall
CADD	23.8	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 0.00441% European (non-Finnish) · 52/1,180,014 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00341% 55/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,693
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Phe504Ser
Coding: c.1511T>C
MANE Select: NM_003567
dbSNP: rs769691162
Type: single nucleotide variant
Location: chr1:93582476 (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-phe504ser (accessed [today's date]).

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