Is BCAN p.Arg599Gln (c.1796G>A) pathogenic?

BCAN p.Arg599Gln (c.1796G>A) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.0615); Very rare (popmax 0.0017%, nfe).

How common is BCAN p.Arg599Gln (c.1796G>A) in the general population?

BCAN p.Arg599Gln (c.1796G>A) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about BCAN p.Arg599Gln (c.1796G>A)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

BCAN p.Arg599Gln

c.1796G>A · rs761504175 · VCV2271571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -3.3
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0017% European (non-Finnish) · 20/1,174,454 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000904%

Overall 0.00137% 22/1,604,768 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,723
Remaining individualsnot grpmax-eligible	0.00161%	61,958
African / African-American	0.00134%	74,534

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.Arg599Gln
Coding: c.1796G>A
MANE Select: NM_021948
dbSNP: rs761504175
Type: single nucleotide variant
Location: chr1:156652746 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 599: the 'disordered' region

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

Similar variants

BCAN p.Arg599Trp 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-arg599gln (accessed [today's date]).

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