Is BCAM p.Lys451Gln (c.1351A>C) pathogenic?

BCAM p.Lys451Gln (c.1351A>C) is classified Likely benign in BCAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-18). AlphaMissense: likely benign (0.0998); Rare (popmax 0.943%, afr); Associated with BCAM-related disorder.

What condition is associated with BCAM p.Lys451Gln (c.1351A>C)?

BCAM p.Lys451Gln (c.1351A>C) is associated with BCAM-related disorder (ClinVar).

How common is BCAM p.Lys451Gln (c.1351A>C) in the general population?

BCAM p.Lys451Gln (c.1351A>C) is rare (popmax 0.943%, afr) (gnomAD).

What do computational predictors say about BCAM p.Lys451Gln (c.1351A>C)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

BCAM p.Lys451Gln

c.1351A>C · rs28399630 · VCV3034205

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.943%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BCAM-related disorder

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -3.98	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 6.6	GERP 1.9, phastCons 0.84
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	13.89	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 0.943% African / African-American · 707/74,964 alleles

Filtering AF 0.886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.863%

Overall 0.0498% 803/1,613,936 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.943%	106
Middle Eastern	0.0825%	1,212
Admixed American	0.0733%	1,363
Remaining individualsnot grpmax-eligible	0.064%	1,563
European (non-Finnish)	0.000593%	168,564

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.Lys451Gln
Coding: c.1351A>C
MANE Select: NM_005581
dbSNP: rs28399630
Type: single nucleotide variant
Location: chr19:44819070 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 451: a UniProt-annotated variant site (in); the ig-like c2-type 3 domain

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

Disease context

BCAM-related disorder

Similar variants

BCAM c.1764-4C>T Likely benign same condition
BCAM c.1882-9G>A Likely benign same condition
BCAM c.433+8T>A Likely benign same condition
BCAM p.Ala238= Benign same condition
BCAM p.Cys237= Benign same condition
BCAM p.Met204Lys Likely benign ⚠ same condition
BCAM p.Pro39Leu Likely benign ⚠ same condition
BCAM p.Ser332= Likely benign same condition

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-lys451gln (accessed [today's date]).

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