Is BACE2 p.Val411= (c.1233G>A) pathogenic?

BACE2 p.Val411= (c.1233G>A) is classified Likely benign in BACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-22). Ultra-rare (popmax 0.0164%, nfe).

How common is BACE2 p.Val411= (c.1233G>A) in the general population?

BACE2 p.Val411= (c.1233G>A) is ultra-rare (popmax 0.0164%, nfe) (gnomAD).

BACE2 p.Val411=

c.1233G>A · rs371254480 · VCV711742

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -1.9, phastCons 0.98
Overall
CADD	9.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% European (non-Finnish) · 194/1,180,046 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.0123% 198/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0164%	6,083
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00267%	37,467

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.Val411=
Coding: c.1233G>A
MANE Select: NM_012105
dbSNP: rs371254480
Type: single nucleotide variant
Location: chr21:41257256 (GRCh38)
Gene constraint: LOEUF 0.574 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 83.31 · 19 PDB
Residue 411: a disulfide bond; the peptidase a1 domain; an α-helix

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-val411 (accessed [today's date]).

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