Is BBOX1 p.Asp70Val (c.209A>T) pathogenic?

BBOX1 p.Asp70Val (c.209A>T) is classified Uncertain significance in BBOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: ambiguous (0.3668); Absent from gnomAD v4.1.

How common is BBOX1 p.Asp70Val (c.209A>T) in the general population?

BBOX1 p.Asp70Val (c.209A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBOX1 p.Asp70Val (c.209A>T)?

AlphaMissense predicts ambiguous (score 0.3668) — an in-silico prediction, not a clinical call.

BBOX1 p.Asp70Val

c.209A>T · rs2494257279 · VCV2608974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3668 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3668	ambiguous
REVEL	0.506	indeterminate
SaProt	LLR -7.72	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 72 kb · p 0.9 · regional, not allelic
Overall
CADD	24.2	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

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.Asp70Val
Coding: c.209A>T
MANE Select: NM_003986
dbSNP: rs2494257279
Type: single nucleotide variant
Location: chr11:27055639 (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-asp70val (accessed [today's date]).

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