Is BACE2 p.Pro32His (c.95C>A) pathogenic?

BACE2 p.Pro32His (c.95C>A) is classified Uncertain significance in BACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: ambiguous (0.4156); Absent from gnomAD v4.1.

How common is BACE2 p.Pro32His (c.95C>A) in the general population?

BACE2 p.Pro32His (c.95C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACE2 p.Pro32His (c.95C>A)?

AlphaMissense predicts ambiguous (score 0.4156) — an in-silico prediction, not a clinical call.

BACE2 p.Pro32His

c.95C>A · rs2516878111 · VCV3132780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4156 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,391,404)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4156	ambiguous
REVEL	0.136	moderately benign-leaning
SaProt	LLR -8.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP -0.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 69 kb · p 0.41 · regional, not allelic
Overall
CADD	21.0	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

No allele count reported in gnomAD v4.1 (AN 1,391,404). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BACE2
Protein: p.Pro32His
Coding: c.95C>A
MANE Select: NM_012105
dbSNP: rs2516878111
Type: single nucleotide variant
Location: chr21:41168358 (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.His56Tyr 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

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-pro32his (accessed [today's date]).

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