Is BACE2 p.His56Tyr (c.166C>T) pathogenic?

BACE2 p.His56Tyr (c.166C>T) is classified Benign in BACE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-20). AlphaMissense: likely benign (0.102); Rare (popmax 0.565%, eas).

How common is BACE2 p.His56Tyr (c.166C>T) in the general population?

BACE2 p.His56Tyr (c.166C>T) is rare (popmax 0.565%, eas) (gnomAD).

What do computational predictors say about BACE2 p.His56Tyr (c.166C>T)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

BACE2 p.His56Tyr

c.166C>T · rs200758268 · VCV724936

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.565%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.62	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 0.09	GERP -2.3
Regional constraint	o/e 0.95	unconstrained · MANE · 69 kb · p 0.41 · regional, not allelic
Overall
CADD	15.74	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 0.565% East Asian · 187/33,082 alleles

Filtering AF 0.499% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.474%

Overall 0.0187% 262/1,398,948 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.565%	177
South Asian	0.078%	1,282
Remaining individualsnot grpmax-eligible	0.044%	2,273
European (non-Finnish)	0.000372%	268,623

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: BACE2
Protein: p.His56Tyr
Coding: c.166C>T
MANE Select: NM_012105
dbSNP: rs200758268
Type: single nucleotide variant
Location: chr21:41168429 (GRCh38)
Gene constraint: LOEUF 0.574 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 83.31 · 19 PDB

Full BACE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BACE2 c.1135-10C>T Benign ★★ same type
BACE2 c.1304-8C>T Benign ★★ same type
BACE2 p.Ser88= Likely benign ★★ same type
BACE2 p.Ala200Gly Uncertain significance ★ ⚠ same type
BACE2 p.Ala25Val Uncertain significance ★ ⚠ same type
BACE2 p.Ala297Thr Uncertain significance ★ ⚠ same type
BACE2 p.Ala36Thr Uncertain significance ★ ⚠ same type
BACE2 p.Ala404Val 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/bace2-p-his56tyr (accessed [today's date]).

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