Is BCAN p.Gly226Arg (c.676G>A) pathogenic?

BCAN p.Gly226Arg (c.676G>A) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely pathogenic (0.9881); Very rare (popmax 0.00892%, eas).

How common is BCAN p.Gly226Arg (c.676G>A) in the general population?

BCAN p.Gly226Arg (c.676G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about BCAN p.Gly226Arg (c.676G>A)?

AlphaMissense predicts likely pathogenic (score 0.9881) — an in-silico prediction, not a clinical call.

BCAN p.Gly226Arg

c.676G>A · VCV3479986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9881	likely pathogenic · top 5% in BCAN
REVEL	0.436	indeterminate
SaProt	LLR -15.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 417 bp · p 0.00028 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,868 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00112% 18/1,613,866 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,217
South Asian	0.00769%	13,010
African / African-American	0.00401%	24,960
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000254%	393,320

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: BCAN
Protein: p.Gly226Arg
Coding: c.676G>A
MANE Select: NM_021948
Type: single nucleotide variant
Location: chr1:156648017 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 226: a disulfide bond; the link 1 domain

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

Similar variants

BCAN p.Arg105Gly Benign ★★ ⚠ same type
BCAN p.Ala10Pro Uncertain significance ★ ⚠ same type
BCAN p.Ala112Thr Uncertain significance ★ ⚠ same type
BCAN p.Ala166Val Uncertain significance ★ ⚠ same type
BCAN p.Ala169Thr Uncertain significance ★ ⚠ same type
BCAN p.Ala2Thr Uncertain significance ★ ⚠ same type
BCAN p.Ala357Thr Uncertain significance ★ ⚠ same type
BCAN p.Ala357Val 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/bcan-p-gly226arg (accessed [today's date]).

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