Is BCAR1 p.Pro141Ser (c.421C>T) pathogenic?

BCAR1 p.Pro141Ser (c.421C>T) is classified Uncertain significance in BCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.0741); Ultra-rare (popmax 0.0124%, afr).

How common is BCAR1 p.Pro141Ser (c.421C>T) in the general population?

BCAR1 p.Pro141Ser (c.421C>T) is ultra-rare (popmax 0.0124%, afr) (gnomAD).

What do computational predictors say about BCAR1 p.Pro141Ser (c.421C>T)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

BCAR1 p.Pro141Ser

c.421C>T · rs776940727 · VCV2266953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -7.17	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 8.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 13 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	23.1	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 0.0124% African / African-American · 9/72,332 alleles

Filtering AF 0.00644% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00065% 10/1,537,544 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0124%	8,037
European (non-Finnish)	8.74e-05%	1,144,235

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: BCAR1
Protein: p.Pro141Ser
Coding: c.421C>T
MANE Select: NM_014567
dbSNP: rs776940727
Type: single nucleotide variant
Location: chr16:75242682 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.07 · 5 PDB
Residue 141: the 'disordered' region; the 'substrate for kinases' region

Full BCAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAR1 c.2100+10C>T Benign/Likely benign ★★ same type
BCAR1 p.Ala411= Benign ★★ same type
BCAR1 p.Ala514= Benign ★★ same type
BCAR1 p.Ala590Thr Benign ★★ ⚠ same type
BCAR1 p.Arg491Leu Benign ★★ same type
BCAR1 p.Gly450Val Benign ★★ same type
BCAR1 p.Gly568Ser Benign ★★ same type
BCAR1 p.His558Arg Benign ★★ 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/bcar1-p-pro141ser (accessed [today's date]).

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