Is BBOX1 p.Phe310= (c.930T>C) pathogenic?

BBOX1 p.Phe310= (c.930T>C) is classified Benign in BBOX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-15). Common (popmax 6.45%, afr) — too common for a highly-penetrant pathogenic allele.

BBOX1 p.Phe310=

Q: How common is BBOX1 p.Phe310= (c.930T>C) in the general population?

BBOX1 p.Phe310= (c.930T>C) is common (popmax 6.45%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.930T>C · rs73434012 · VCV778515

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.45%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP -4, phastCons 0.25
Overall
CADD	5.811	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.45% African / African-American · 4,841/75,010 alleles

Filtering AF 6.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.24%

Overall 0.473% 7,636/1,613,864 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.45%	15
Ashkenazi Jewishnot grpmax-eligible	3.94%	25
Remaining individualsnot grpmax-eligible	0.854%	117
Middle Eastern	0.512%	195
Admixed American	0.419%	239
European (non-Finnish)	0.0673%	1,486
South Asian	0.0209%	4,792
East Asian	0.00223%	44,854

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.Phe310=
Coding: c.930T>C
MANE Select: NM_003986
dbSNP: rs73434012
Type: single nucleotide variant
Location: chr11:27125747 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 12 PDB
Residue 310: an α-helix

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

Similar variants

BBOX1 p.Ala207= 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
BBOX1 p.Arg288Cys 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-phe310 (accessed [today's date]).

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