Is BCAN p.Arg669Cys (c.2005C>T) pathogenic?

BCAN p.Arg669Cys (c.2005C>T) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely benign (0.1818); Very rare (popmax 0.00523%, nfe).

How common is BCAN p.Arg669Cys (c.2005C>T) in the general population?

BCAN p.Arg669Cys (c.2005C>T) is very rare (popmax 0.00523%, nfe) (gnomAD).

What do computational predictors say about BCAN p.Arg669Cys (c.2005C>T)?

AlphaMissense predicts likely benign (score 0.1818) — an in-silico prediction, not a clinical call.

BCAN p.Arg669Cys

c.2005C>T · rs775100384 · VCV3133217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00523%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1818	likely benign
REVEL	0.566	indeterminate
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	27.2	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 0.00523% European (non-Finnish) · 57/1,090,504 alleles

Filtering AF 0.00408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00373%

Overall 0.00423% 60/1,418,466 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00523%	19,132
Admixed American	0.003%	33,386
South Asian	0.00195%	51,362
Remaining individualsnot grpmax-eligible	0.00187%	53,592

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.Arg669Cys
Coding: c.2005C>T
MANE Select: NM_021948
dbSNP: rs775100384
Type: single nucleotide variant
Location: chr1:156656344 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 669: a disulfide bond; the egf-like domain

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

Similar variants

BCAN p.Arg669His 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-arg669cys (accessed [today's date]).

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