Is BCAM p.Asp343Asn (c.1027G>A) pathogenic?

BCAM p.Asp343Asn (c.1027G>A) is classified Uncertain significance in BCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-02). AlphaMissense: ambiguous (0.3901); Very rare (popmax 0.00636%, nfe).

How common is BCAM p.Asp343Asn (c.1027G>A) in the general population?

BCAM p.Asp343Asn (c.1027G>A) is very rare (popmax 0.00636%, nfe) (gnomAD).

What do computational predictors say about BCAM p.Asp343Asn (c.1027G>A)?

AlphaMissense predicts ambiguous (score 0.3901) — an in-silico prediction, not a clinical call.

BCAM p.Asp343Asn

c.1027G>A · VCV3990831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3901	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -3.06	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	24.9	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 0.00636% European (non-Finnish) · 75/1,180,014 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.0049% 79/1,613,806 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,734
Admixed American	0.00333%	29,991
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00157%	63,848

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.Asp343Asn
Coding: c.1027G>A
MANE Select: NM_005581
Type: single nucleotide variant
Location: chr19:44814709 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 343: the ig-like c2-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-asp343asn (accessed [today's date]).

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