Is BCAM p.Arg357His (c.1070G>A) pathogenic?

BCAM p.Arg357His (c.1070G>A) is classified Likely benign in BCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.0615); Ultra-rare (popmax 0.0134%, eas).

How common is BCAM p.Arg357His (c.1070G>A) in the general population?

BCAM p.Arg357His (c.1070G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about BCAM p.Arg357His (c.1070G>A)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

BCAM p.Arg357His

c.1070G>A · rs777905118 · VCV2319562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.44	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 -1.3	GERP -3.5
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	2.524	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 0.0134% East Asian · 6/44,860 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00143% 23/1,610,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,477
Remaining individualsnot grpmax-eligible	0.00481%	20,777
South Asian	0.0044%	22,742
Admixed American	0.00167%	59,904
European (non-Finnish)	0.000763%	130,983

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.Arg357His
Coding: c.1070G>A
MANE Select: NM_005581
dbSNP: rs777905118
Type: single nucleotide variant
Location: chr19:44814752 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB

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-arg357his (accessed [today's date]).

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