Is BCAN p.Asp679His (c.2035G>C) pathogenic?

BCAN p.Asp679His (c.2035G>C) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.0999); Ultra-rare (popmax 0.0453%, amr).

How common is BCAN p.Asp679His (c.2035G>C) in the general population?

BCAN p.Asp679His (c.2035G>C) is ultra-rare (popmax 0.0453%, amr) (gnomAD).

What do computational predictors say about BCAN p.Asp679His (c.2035G>C)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

BCAN p.Asp679His

c.2035G>C · rs201179524 · VCV3133219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	17.51	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 0.0453% Admixed American · 15/33,100 alleles

Filtering AF 0.0279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.0158% 218/1,380,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.548%	182
Admixed Americangrpmax	0.0453%	2,207
Remaining individualsnot grpmax-eligible	0.029%	3,449
European (non-Finnish)	0.017%	5,880
Finnishnot grpmax-eligible	0.00177%	56,528
African / African-American	0.0015%	66,828

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp679His
Coding: c.2035G>C
MANE Select: NM_021948
dbSNP: rs201179524
Type: single nucleotide variant
Location: chr1:156656374 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 679: 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.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-asp679his (accessed [today's date]).

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