Is BBOX1 p.Phe201Ser (c.602T>C) pathogenic?

BBOX1 p.Phe201Ser (c.602T>C) is classified Uncertain significance in BBOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.7103); Ultra-rare (popmax 0.0319%, sas).

How common is BBOX1 p.Phe201Ser (c.602T>C) in the general population?

BBOX1 p.Phe201Ser (c.602T>C) is ultra-rare (popmax 0.0319%, sas) (gnomAD).

What do computational predictors say about BBOX1 p.Phe201Ser (c.602T>C)?

AlphaMissense predicts likely pathogenic (score 0.7103) — an in-silico prediction, not a clinical call.

BBOX1 p.Phe201Ser

c.602T>C · VCV4645315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7103 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7103	likely pathogenic
REVEL	0.707	pathogenic-leaning
SaProt	LLR -9.37	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 72 kb · p 0.9 · regional, not allelic
Overall
CADD	29.3	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 0.0319% South Asian · 29/90,946 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00186% 30/1,611,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0319%	3,136
Remaining individualsnot grpmax-eligible	0.0016%	62,342

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: BBOX1
Protein: p.Phe201Ser
Coding: c.602T>C
MANE Select: NM_003986
Type: single nucleotide variant
Location: chr11:27115520 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 12 PDB
Residue 201: a β-strand

Full BBOX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BBOX1 p.Ala207= Benign ★★ same type
BBOX1 p.Phe310= Benign ★★ same type
BBOX1 p.Tyr133= Benign ★★ same type
BBOX1 p.Ala14Asp Uncertain significance ★ ⚠ same type
BBOX1 p.Ala155Thr Uncertain significance ★ ⚠ same type
BBOX1 p.Ala193Ser Uncertain significance ★ ⚠ same type
BBOX1 p.Ala248Val Uncertain significance ★ ⚠ same type
BBOX1 p.Ala354Thr 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/bbox1-p-phe201ser (accessed [today's date]).

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