Is BOP1 p.Ser50Phe (c.149C>T) pathogenic?

BOP1 p.Ser50Phe (c.149C>T) is classified Uncertain significance in BOP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.0979); Very rare (popmax 0.00667%, afr).

How common is BOP1 p.Ser50Phe (c.149C>T) in the general population?

BOP1 p.Ser50Phe (c.149C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about BOP1 p.Ser50Phe (c.149C>T)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

BOP1 p.Ser50Phe

c.149C>T · VCV3261352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -9.04	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 6.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.0028 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,914 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00329% 5/152,204 alleles · very rare

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.Ser50Phe
Coding: c.149C>T
MANE Select: NM_015201
Type: single nucleotide variant
Location: chr8:144289255 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 10 PDB
Residue 50: 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.Arg20Trp 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

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-ser50phe (accessed [today's date]).

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