Is BOC p.Ser366Asn (c.1097G>A) pathogenic?

BOC p.Ser366Asn (c.1097G>A) is classified Uncertain significance in BOC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely pathogenic (0.6415); Rare (popmax 0.346%, mid).

How common is BOC p.Ser366Asn (c.1097G>A) in the general population?

BOC p.Ser366Asn (c.1097G>A) is rare (popmax 0.346%, mid) (gnomAD).

What do computational predictors say about BOC p.Ser366Asn (c.1097G>A)?

AlphaMissense predicts likely pathogenic (score 0.6415) — an in-silico prediction, not a clinical call.

BOC p.Ser366Asn

c.1097G>A · rs148670622 · VCV2362652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6415 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.346%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6415	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.40	acceptor loss · deltas
Pangolin	Δ0.26	gain · loss 0.00 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 5.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	22.8	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 0.346% Middle Eastern · 21/6,062 alleles

Filtering AF 0.232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.00768% 124/1,613,850 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.346%	289
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	0.00754%	13,259
South Asian	0.00439%	22,771
African / African-American	0.00267%	37,523
East Asian	0.00223%	44,858
Admixed American	0.00167%	60,020
Finnishnot grpmax-eligible	0.00157%	63,746

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.Ser366Asn
Coding: c.1097G>A
MANE Select: NM_001378074
dbSNP: rs148670622
Type: single nucleotide variant
Location: chr3:113273204 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.98 · 3 PDB
Residue 366: a disulfide bond; 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-ser366asn (accessed [today's date]).

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