Is BBOX1 p.Asp336Val (c.1007A>T) pathogenic?

BBOX1 p.Asp336Val (c.1007A>T) is classified Uncertain significance in BBOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely pathogenic (0.8835); Absent from gnomAD v4.1.

How common is BBOX1 p.Asp336Val (c.1007A>T) in the general population?

BBOX1 p.Asp336Val (c.1007A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBOX1 p.Asp336Val (c.1007A>T)?

AlphaMissense predicts likely pathogenic (score 0.8835) — an in-silico prediction, not a clinical call.

BBOX1 p.Asp336Val

c.1007A>T · rs2494523479 · VCV2253676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8835	likely pathogenic
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -14.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 72 kb · p 0.9 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBOX1
Protein: p.Asp336Val
Coding: c.1007A>T
MANE Select: NM_003986
dbSNP: rs2494523479
Type: single nucleotide variant
Location: chr11:27127296 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 12 PDB

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-asp336val (accessed [today's date]).

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