Is BOC p.Arg513His (c.1538G>A) pathogenic?

BOC p.Arg513His (c.1538G>A) is classified Uncertain significance in BOC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: ambiguous (0.5215); Ultra-rare (popmax 0.0135%, sas).

How common is BOC p.Arg513His (c.1538G>A) in the general population?

BOC p.Arg513His (c.1538G>A) is ultra-rare (popmax 0.0135%, sas) (gnomAD).

What do computational predictors say about BOC p.Arg513His (c.1538G>A)?

AlphaMissense predicts ambiguous (score 0.5215) — an in-silico prediction, not a clinical call.

BOC p.Arg513His

c.1538G>A · VCV4214705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5215 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, sas)

Computational evidence

Protein change
AlphaMissense	0.5215	ambiguous
REVEL	0.553	indeterminate
SaProt	LLR -10.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	29.2	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 0.0135% South Asian · 12/88,866 alleles

Filtering AF 0.00778% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00607%

Overall 0.00201% 32/1,589,284 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0135%	7,405
African / African-American	0.00671%	14,912
Remaining individualsnot grpmax-eligible	0.0049%	20,419
Finnishnot grpmax-eligible	0.00159%	63,032
European (non-Finnish)	0.000946%	105,747

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.Arg513His
Coding: c.1538G>A
MANE Select: NM_001378074
Type: single nucleotide variant
Location: chr3:113274678 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.98 · 3 PDB
Residue 513: the fibronectin type-iii 1 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-arg513his (accessed [today's date]).

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