Is BOC p.Arg570Trp (c.1708C>T) pathogenic?

BOC p.Arg570Trp (c.1708C>T) is classified Uncertain significance in BOC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely benign (0.3159); Very rare (popmax 0.00513%, nfe).

How common is BOC p.Arg570Trp (c.1708C>T) in the general population?

BOC p.Arg570Trp (c.1708C>T) is very rare (popmax 0.00513%, nfe) (gnomAD).

What do computational predictors say about BOC p.Arg570Trp (c.1708C>T)?

AlphaMissense predicts likely benign (score 0.3159) — an in-silico prediction, not a clinical call.

BOC p.Arg570Trp

c.1708C>T · rs763721866 · VCV2469669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3159 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00513%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3159	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	27.5	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 R569W vs ClinVar R570W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00513% European (non-Finnish) · 59/1,151,062 alleles

Filtering AF 0.00404% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0037%

Overall 0.00391% 61/1,559,072 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00513%	19,510
South Asian	0.00237%	42,264

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.Arg570Trp
Coding: c.1708C>T
MANE Select: NM_001378074
dbSNP: rs763721866
Type: single nucleotide variant
Location: chr3:113278675 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.98 · 3 PDB
Residue 570: 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-arg570trp (accessed [today's date]).

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