Is BOC p.Pro913Ser (c.2737C>T) pathogenic?

BOC p.Pro913Ser (c.2737C>T) is classified Benign in BOC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-12). AlphaMissense: likely benign (0.1016); Low-frequency (popmax 3.45%, eas).

How common is BOC p.Pro913Ser (c.2737C>T) in the general population?

BOC p.Pro913Ser (c.2737C>T) is low-frequency (popmax 3.45%, eas) (gnomAD).

What do computational predictors say about BOC p.Pro913Ser (c.2737C>T)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

BOC p.Pro913Ser

c.2737C>T · rs3814404 · VCV713904

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.45%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.39, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	16.71	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P912S vs ClinVar P913S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.45% East Asian · 1,550/44,880 alleles

Filtering AF 3.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.25%

Overall 0.102% 1,647/1,614,244 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.45%	29
Remaining individualsnot grpmax-eligible	0.134%	744
African / African-American	0.004%	25,022
Admixed American	0.00333%	30,015
South Asian	0.00329%	30,363
European (non-Finnish)	0.000424%	236,007

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.Pro913Ser
Coding: c.2737C>T
MANE Select: NM_001378074
dbSNP: rs3814404
Type: single nucleotide variant
Location: chr3:113284415 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.98 · 3 PDB

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

Similar variants

BOC p.Pro913Ala Uncertain significance ★ ⚠ same residue
BOC p.Ala715= Benign ★★ same type
BOC p.Lys884Asn Benign ★★ ⚠ same type
BOC p.Pro829Arg 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-pro913ser (accessed [today's date]).

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