Is BDH2 p.Gly88Glu (c.263G>A) pathogenic?

BDH2 p.Gly88Glu (c.263G>A) is classified Uncertain significance in BDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely pathogenic (0.906); Absent from gnomAD v4.1.

How common is BDH2 p.Gly88Glu (c.263G>A) in the general population?

BDH2 p.Gly88Glu (c.263G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BDH2 p.Gly88Glu (c.263G>A)?

AlphaMissense predicts likely pathogenic (score 0.906) — an in-silico prediction, not a clinical call.

BDH2 p.Gly88Glu

c.263G>A · rs2477105301 · VCV2482154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.906	likely pathogenic
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -9.77	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 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 0.0025 · regional, not allelic
Overall
CADD	28.0	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: BDH2
Protein: p.Gly88Glu
Coding: c.263G>A
MANE Select: NM_020139
dbSNP: rs2477105301
Type: single nucleotide variant
Location: chr4:103091271 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 1 PDB

Full BDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BDH2 p.Thr182= Benign ★★ same type
BDH2 p.Ala14Thr Uncertain significance ★ ⚠ same type
BDH2 p.Ala23Pro Uncertain significance ★ ⚠ same type
BDH2 p.Ala27Val Uncertain significance ★ ⚠ same type
BDH2 p.Arg199Trp Uncertain significance ★ ⚠ same type
BDH2 p.Arg3Gln Uncertain significance ★ ⚠ same type
BDH2 p.Arg55Cys Uncertain significance ★ ⚠ same type
BDH2 p.Arg55His 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/bdh2-p-gly88glu (accessed [today's date]).

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