Is BCAR3 p.Val707Phe (c.2119G>T) pathogenic?

BCAR3 p.Val707Phe (c.2119G>T) is classified Uncertain significance in BCAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: likely benign (0.2697); Ultra-rare (popmax 0.0106%, nfe).

How common is BCAR3 p.Val707Phe (c.2119G>T) in the general population?

BCAR3 p.Val707Phe (c.2119G>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

What do computational predictors say about BCAR3 p.Val707Phe (c.2119G>T)?

AlphaMissense predicts likely benign (score 0.2697) — an in-silico prediction, not a clinical call.

BCAR3 p.Val707Phe

c.2119G>T · VCV3990888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2697 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2697	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -5.38	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	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 113 kb · p 0.0058 · regional, not allelic
Overall
CADD	20.7	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 0.0106% European (non-Finnish) · 125/1,180,054 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00844%

Overall 0.00787% 127/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,440
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,938

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.Val707Phe
Coding: c.2119G>T
MANE Select: NM_003567
Type: single nucleotide variant
Location: chr1:93567459 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.36 · 1 PDB
Residue 707: the ras-gef 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-val707phe (accessed [today's date]).

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