Is BCAR1 p.Pro85Ser (c.253C>T) pathogenic?

BCAR1 p.Pro85Ser (c.253C>T) is classified Uncertain significance in BCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0683); Absent from gnomAD v4.1.

How common is BCAR1 p.Pro85Ser (c.253C>T) in the general population?

BCAR1 p.Pro85Ser (c.253C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAR1 p.Pro85Ser (c.253C>T)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

BCAR1 p.Pro85Ser

c.253C>T · VCV4645374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.45	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 1.7	GERP -3.9, phastCons 0.95
Regional constraint	o/e 1.12	unconstrained · MANE · 13 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	17.57	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCAR1
Protein: p.Pro85Ser
Coding: c.253C>T
MANE Select: NM_014567
Type: single nucleotide variant
Location: chr16:75242850 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.07 · 5 PDB
Residue 85: the 'disordered' 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-pro85ser (accessed [today's date]).

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