Is BCAN p.Arg36Cys (c.106C>T) pathogenic?

BCAN p.Arg36Cys (c.106C>T) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.3151); Very rare (popmax 0.000346%, nfe).

How common is BCAN p.Arg36Cys (c.106C>T) in the general population?

BCAN p.Arg36Cys (c.106C>T) is very rare (popmax 0.000346%, nfe) (gnomAD).

What do computational predictors say about BCAN p.Arg36Cys (c.106C>T)?

AlphaMissense predicts likely benign (score 0.3151) — an in-silico prediction, not a clinical call.

BCAN p.Arg36Cys

c.106C>T · VCV3822607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3151 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000346%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3151	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.63	GERP -4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,593 bp · p 0.91 · regional, not allelic
Overall
CADD	24.6	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 0.000346% European (non-Finnish) · 4/1,156,922 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000283% 4/1,414,734 alleles · very rare

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.Arg36Cys
Coding: c.106C>T
MANE Select: NM_021948
Type: single nucleotide variant
Location: chr1:156646815 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 36: the ig-like v-type 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-arg36cys (accessed [today's date]).

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