Is BCAM p.Val386Met (c.1156G>A) pathogenic?

BCAM p.Val386Met (c.1156G>A) is classified Uncertain significance in BCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.2488); Ultra-rare (popmax 0.0659%, sas).

How common is BCAM p.Val386Met (c.1156G>A) in the general population?

BCAM p.Val386Met (c.1156G>A) is ultra-rare (popmax 0.0659%, sas) (gnomAD).

What do computational predictors say about BCAM p.Val386Met (c.1156G>A)?

AlphaMissense predicts likely benign (score 0.2488) — an in-silico prediction, not a clinical call.

BCAM p.Val386Met

c.1156G>A · rs138302587 · VCV3133198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2488 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2488	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -12.02	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.62, phastCons 0.065
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	23.1	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 0.0659% South Asian · 60/91,086 alleles

Filtering AF 0.0525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0476%

Overall 0.0062% 100/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0659%	1,518
East Asian	0.0178%	5,610
Finnishnot grpmax-eligible	0.0141%	7,115
Remaining individualsnot grpmax-eligible	0.008%	12,500
African / African-American	0.00533%	18,752
European (non-Finnish)	0.00119%	84,283

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.Val386Met
Coding: c.1156G>A
MANE Select: NM_005581
dbSNP: rs138302587
Type: single nucleotide variant
Location: chr19:44818599 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 386: a disulfide bond; the ig-like c2-type 2 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-val386met (accessed [today's date]).

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