Is BOC p.Ser353= (c.1059C>T) pathogenic?

BOC p.Ser353= (c.1059C>T) is classified Likely benign in BOC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Ultra-rare (popmax 0.0617%, amr).

How common is BOC p.Ser353= (c.1059C>T) in the general population?

BOC p.Ser353= (c.1059C>T) is ultra-rare (popmax 0.0617%, amr) (gnomAD).

BOC p.Ser353=

c.1059C>T · rs144269826 · VCV2654037

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, amr)

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 -20	GERP -4.2
Overall
CADD	2.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0617% Admixed American · 37/60,012 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.0136% 220/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0617%	1,622
Remaining individualsnot grpmax-eligible	0.0208%	4,806
European (non-Finnish)	0.0136%	7,329
East Asian	0.00891%	11,219
African / African-American	0.004%	24,984
South Asian	0.0022%	45,541

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.Ser353=
Coding: c.1059C>T
MANE Select: NM_001378074
dbSNP: rs144269826
Type: single nucleotide variant
Location: chr3:113273166 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.98 · 3 PDB
Residue 353: 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-ser353 (accessed [today's date]).

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