Is BOP1 p.Arg20Trp (c.58C>T) pathogenic?

BOP1 p.Arg20Trp (c.58C>T) is classified Uncertain significance in BOP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely benign (0.3276); Ultra-rare (popmax 0.041%, nfe).

How common is BOP1 p.Arg20Trp (c.58C>T) in the general population?

BOP1 p.Arg20Trp (c.58C>T) is ultra-rare (popmax 0.041%, nfe) (gnomAD).

What do computational predictors say about BOP1 p.Arg20Trp (c.58C>T)?

AlphaMissense predicts likely benign (score 0.3276) — an in-silico prediction, not a clinical call.

BOP1 p.Arg20Trp

c.58C>T · VCV3261351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3276 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.041%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3276	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.23, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.0028 · regional, not allelic
Overall
CADD	23.8	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 0.041% European (non-Finnish) · 449/1,096,264 alleles

Filtering AF 0.0378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.0332% 479/1,440,696 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.041%	2,442
Remaining individualsnot grpmax-eligible	0.0276%	3,624
Admixed American	0.0151%	6,605
African / African-American	0.0119%	8,401
Finnishnot grpmax-eligible	0.00219%	45,696

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: BOP1
Protein: p.Arg20Trp
Coding: c.58C>T
MANE Select: NM_015201
Type: single nucleotide variant
Location: chr8:144291313 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 10 PDB
Residue 20: the 'disordered' region

Full BOP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BOP1 p.Ala7Val Uncertain significance ★ ⚠ same type
BOP1 p.Arg21Gln Uncertain significance ★ ⚠ same type
BOP1 p.Arg568Cys Uncertain significance ★ ⚠ same type
BOP1 p.Arg576Cys Uncertain significance ★ ⚠ same type
BOP1 p.Arg576His Uncertain significance ★ ⚠ same type
BOP1 p.Arg577His Uncertain significance ★ ⚠ same type
BOP1 p.Arg591Gln Uncertain significance ★ ⚠ same type
BOP1 p.Asp54Asn 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/bop1-p-arg20trp (accessed [today's date]).

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