Is BOC p.Glu394Lys (c.1180G>A) pathogenic?

BOC p.Glu394Lys (c.1180G>A) is classified Uncertain significance in BOC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: ambiguous (0.437); Ultra-rare (popmax 0.0635%, amr).

How common is BOC p.Glu394Lys (c.1180G>A) in the general population?

BOC p.Glu394Lys (c.1180G>A) is ultra-rare (popmax 0.0635%, amr) (gnomAD).

What do computational predictors say about BOC p.Glu394Lys (c.1180G>A)?

AlphaMissense predicts ambiguous (score 0.437) — an in-silico prediction, not a clinical call.

BOC p.Glu394Lys

c.1180G>A · VCV4646314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.437 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0635%, amr)

Computational evidence

Protein change
AlphaMissense	0.437	ambiguous
REVEL	0.392	indeterminate
SaProt	LLR -7.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	28.0	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

Grpmax group 0.0635% Admixed American · 38/59,850 alleles

Filtering AF 0.0475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.042%

Overall 0.00305% 49/1,606,136 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0635%	1,575
African / African-American	0.00134%	74,820
South Asian	0.0011%	90,902
European (non-Finnish)	0.000766%	130,478

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: BOC
Protein: p.Glu394Lys
Coding: c.1180G>A
MANE Select: NM_001378074
Type: single nucleotide variant
Location: chr3:113273287 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.98 · 3 PDB
Residue 394: the ig-like c2-type 4 domain

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

Similar variants

BOC p.Ala715= Benign ★★ same type
BOC p.Lys884Asn Benign ★★ ⚠ same type
BOC p.Pro829Arg Benign ★★ ⚠ same type
BOC p.Pro913Ser Benign ★★ same type
BOC p.Ala226Thr Uncertain significance ★ ⚠ same type
BOC p.Ala424Thr Uncertain significance ★ ⚠ same type
BOC p.Ala470Val Uncertain significance ★ ⚠ same type
BOC p.Ala503Val 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/boc-p-glu394lys (accessed [today's date]).

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