Is BCAN p.Ala562Ser (c.1684G>T) pathogenic?

BCAN p.Ala562Ser (c.1684G>T) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0773); Very rare (popmax 0.000509%, nfe).

How common is BCAN p.Ala562Ser (c.1684G>T) in the general population?

BCAN p.Ala562Ser (c.1684G>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about BCAN p.Ala562Ser (c.1684G>T)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

BCAN p.Ala562Ser

c.1684G>T · VCV4645342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.61	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 3.2	GERP -0.51, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	15.71	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 0.000509% European (non-Finnish) · 6/1,179,864 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,602 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.Ala562Ser
Coding: c.1684G>T
MANE Select: NM_021948
Type: single nucleotide variant
Location: chr1:156652634 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 562: the 'disordered' region

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-ala562ser (accessed [today's date]).

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