Is BDH2 p.Glu29Asp (c.87A>C) pathogenic?

BDH2 p.Glu29Asp (c.87A>C) is classified Benign in BDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-16). AlphaMissense: likely pathogenic (0.8158); Low-frequency (popmax 2.79%, afr).

How common is BDH2 p.Glu29Asp (c.87A>C) in the general population?

BDH2 p.Glu29Asp (c.87A>C) is low-frequency (popmax 2.79%, afr) (gnomAD).

What do computational predictors say about BDH2 p.Glu29Asp (c.87A>C)?

AlphaMissense predicts likely pathogenic (score 0.8158) — an in-silico prediction, not a clinical call.

BDH2 p.Glu29Asp

c.87A>C · rs76142480 · VCV788978

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8158 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.79%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8158	likely pathogenic
REVEL	0.609	indeterminate
SaProt	LLR -11.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 0.0025 · 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

Grpmax group 2.79% African / African-American · 2,095/75,010 alleles

Filtering AF 2.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.65%

Overall 0.143% 2,310/1,613,482 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.79%	36
Remaining individualsnot grpmax-eligible	0.16%	625
Admixed American	0.148%	674
Middle Eastern	0.0496%	2,015
South Asian	0.00329%	30,358
European (non-Finnish)	0.0017%	58,978

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: BDH2
Protein: p.Glu29Asp
Coding: c.87A>C
MANE Select: NM_020139
dbSNP: rs76142480
Type: single nucleotide variant
Location: chr4:103095267 (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-glu29asp (accessed [today's date]).

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