Is BCAM p.Arg77His (c.230G>A) pathogenic?

BCAM p.Arg77His (c.230G>A) is classified Benign in BCAM (ClinVar, Single submitter, 2 submitters). AlphaMissense: likely benign (0.1052); Low-frequency (popmax 3.25%, nfe).

How common is BCAM p.Arg77His (c.230G>A) in the general population?

BCAM p.Arg77His (c.230G>A) is low-frequency (popmax 3.25%, nfe) (gnomAD).

What do computational predictors say about BCAM p.Arg77His (c.230G>A)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

BCAM p.Arg77His

c.230G>A · rs28399653 · VCV438

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.25%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -11.23	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 -2.3	GERP -2.7
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	2.762	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 3.25% European (non-Finnish) · 38,273/1,177,448 alleles

Filtering AF 3.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.21%

Overall 2.8% 44,875/1,602,760 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.25%	31
African / African-American	2.91%	34
Ashkenazi Jewishnot grpmax-eligible	2.64%	38
Remaining individualsnot grpmax-eligible	2.55%	39
Admixed American	1.86%	54
Middle Eastern	1.45%	69
Finnishnot grpmax-eligible	1.28%	78
Amishnot grpmax-eligible	0.658%	152
South Asian	0.186%	537
East Asian	0.00446%	22,409

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.Arg77His
Coding: c.230G>A
MANE Select: NM_005581
dbSNP: rs28399653
Type: single nucleotide variant
Location: chr19:44812188 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 77: a disulfide bond; a UniProt-annotated variant site (defines the lu(a) antigen); 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-arg77his (accessed [today's date]).

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