Is BACE1 p.Arg255Trp (c.763C>T) pathogenic?

BACE1 p.Arg255Trp (c.763C>T) is classified Uncertain significance in BACE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: ambiguous (0.5185); Ultra-rare (popmax 0.0713%, eas).

How common is BACE1 p.Arg255Trp (c.763C>T) in the general population?

BACE1 p.Arg255Trp (c.763C>T) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

What do computational predictors say about BACE1 p.Arg255Trp (c.763C>T)?

AlphaMissense predicts ambiguous (score 0.5185) — an in-silico prediction, not a clinical call.

BACE1 p.Arg255Trp

c.763C>T · rs571508692 · VCV3132769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5185 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Computational evidence

Protein change
AlphaMissense	0.5185	ambiguous
REVEL	0.326	indeterminate
SaProt	LLR -8.50	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 26 kb · p 2.5e-11 · regional, not allelic
Overall
CADD	29.3	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 0.0713% East Asian · 32/44,884 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00285% 46/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0713%	1,403
South Asian	0.0022%	45,531
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000847%	118,000

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: BACE1
Protein: p.Arg255Trp
Coding: c.763C>T
MANE Select: NM_012104
dbSNP: rs571508692
Type: single nucleotide variant
Location: chr11:117293131 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 87.75 · 431 PDB
Residue 255: a disulfide bond; the peptidase a1 domain; a β-strand

Full BACE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BACE1 p.Arg255Gln Uncertain significance ★ ⚠ same residue
BACE1 p.Ala104Asp Uncertain significance ★ ⚠ same type
BACE1 p.Ala185Val Uncertain significance ★ ⚠ same type
BACE1 p.Ala304Pro Uncertain significance ★ ⚠ same type
BACE1 p.Ala312Val Uncertain significance ★ ⚠ same type
BACE1 p.Ala409Val Uncertain significance ★ ⚠ same type
BACE1 p.Ala459Asp Uncertain significance ★ ⚠ same type
BACE1 p.Arg122Gln 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/bace1-p-arg255trp (accessed [today's date]).

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