Is BCAN p.Arg86Trp (c.256C>T) pathogenic?

BCAN p.Arg86Trp (c.256C>T) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.1755); Ultra-rare (popmax 0.0214%, nfe).

How common is BCAN p.Arg86Trp (c.256C>T) in the general population?

BCAN p.Arg86Trp (c.256C>T) is ultra-rare (popmax 0.0214%, nfe) (gnomAD).

What do computational predictors say about BCAN p.Arg86Trp (c.256C>T)?

AlphaMissense predicts likely benign (score 0.1755) — an in-silico prediction, not a clinical call.

BCAN p.Arg86Trp

c.256C>T · rs376527030 · VCV2377059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1755 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1755	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -11.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP -0.25, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,593 bp · p 0.91 · regional, not allelic
Overall
CADD	25.5	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 0.0214% European (non-Finnish) · 252/1,179,586 alleles

Filtering AF 0.0192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.0179% 289/1,612,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0214%	4,681
South Asian	0.0165%	6,068
Remaining individualsnot grpmax-eligible	0.016%	6,245
Finnishnot grpmax-eligible	0.00946%	10,572
Admixed American	0.005%	19,985
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,544
African / African-American	0.00267%	37,460

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.Arg86Trp
Coding: c.256C>T
MANE Select: NM_021948
dbSNP: rs376527030
Type: single nucleotide variant
Location: chr1:156646965 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 86: the ig-like v-type domain; a disulfide bond

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-arg86trp (accessed [today's date]).

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