Is BCAN p.Arg167His (c.500G>A) pathogenic?

BCAN p.Arg167His (c.500G>A) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.8666); Ultra-rare (popmax 0.0181%, mid).

How common is BCAN p.Arg167His (c.500G>A) in the general population?

BCAN p.Arg167His (c.500G>A) is ultra-rare (popmax 0.0181%, mid) (gnomAD).

What do computational predictors say about BCAN p.Arg167His (c.500G>A)?

AlphaMissense predicts likely pathogenic (score 0.8666) — an in-silico prediction, not a clinical call.

BCAN p.Arg167His

c.500G>A · rs148799690 · VCV2375734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8666	likely pathogenic
REVEL	0.486	indeterminate
SaProt	LLR -10.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,593 bp · p 0.91 · regional, not allelic
Overall
CADD	35.0	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 0.0181% Middle Eastern · 1/5,534 alleles

Filtering AF 0.00276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00362% 58/1,600,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0181%	5,534
Remaining individualsnot grpmax-eligible	0.00808%	12,371
East Asian	0.00446%	22,406
African / African-American	0.00404%	24,751
European (non-Finnish)	0.00366%	27,312
Admixed American	0.00349%	28,656
South Asian	0.00225%	44,510

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.Arg167His
Coding: c.500G>A
MANE Select: NM_021948
dbSNP: rs148799690
Type: single nucleotide variant
Location: chr1:156647541 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 167: the link 1 domain

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

Similar variants

BCAN p.Arg167Leu Uncertain significance ★ ⚠ same residue
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

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-arg167his (accessed [today's date]).

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