Is BCAN p.Pro817Leu (c.2450C>T) pathogenic?

BCAN p.Pro817Leu (c.2450C>T) is classified Uncertain significance in BCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.005%, amr).

How common is BCAN p.Pro817Leu (c.2450C>T) in the general population?

BCAN p.Pro817Leu (c.2450C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about BCAN p.Pro817Leu (c.2450C>T)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

BCAN p.Pro817Leu

c.2450C>T · rs762033515 · VCV3133221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -9.73	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 4.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	27.0	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 0.005% Admixed American · 3/59,988 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00372% 60/1,613,476 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,996
East Asian	0.00446%	22,446
European (non-Finnish)	0.00441%	22,689
Remaining individualsnot grpmax-eligible	0.0032%	31,233
African / African-American	0.00133%	74,916

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.Pro817Leu
Coding: c.2450C>T
MANE Select: NM_021948
dbSNP: rs762033515
Type: single nucleotide variant
Location: chr1:156658555 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 817: a disulfide bond; the sushi 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-pro817leu (accessed [today's date]).

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