Is BCAM p.Glu65Asp (c.195A>C) pathogenic?

BCAM p.Glu65Asp (c.195A>C) is classified Uncertain significance in BCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: ambiguous (0.394); Ultra-rare (popmax 0.0264%, sas).

How common is BCAM p.Glu65Asp (c.195A>C) in the general population?

BCAM p.Glu65Asp (c.195A>C) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

What do computational predictors say about BCAM p.Glu65Asp (c.195A>C)?

AlphaMissense predicts ambiguous (score 0.394) — an in-silico prediction, not a clinical call.

BCAM p.Glu65Asp

c.195A>C · VCV3479970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.394 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.394	ambiguous
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -3.6, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	17.37	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 0.0264% South Asian · 24/91,010 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00168% 27/1,610,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0264%	3,792
African / African-American	0.00268%	37,322
Remaining individualsnot grpmax-eligible	0.00161%	62,258

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: BCAM
Protein: p.Glu65Asp
Coding: c.195A>C
MANE Select: NM_005581
Type: single nucleotide variant
Location: chr19:44811337 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 65: a disulfide bond; a β-strand; the ig-like v-type 1 domain

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

Similar variants

BCAM p.Arg282His Benign ★★ ⚠ same type
BCAM p.Leu409= Benign ★★ same type
BCAM p.Pro589Leu Likely benign ★★ same type
BCAM p.Thr539Ala Benign ★★ same type
BCAM p.Val381Ile Benign ★★ ⚠ same type
BCAM p.Val540= Benign ★★ same type
BCAM p.Ala129Ser Uncertain significance ★ ⚠ same type
BCAM p.Ala129Thr 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/bcam-p-glu65asp (accessed [today's date]).

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