Is BDH2 p.Arg3Gln (c.8G>A) pathogenic?

BDH2 p.Arg3Gln (c.8G>A) is classified Uncertain significance in BDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: ambiguous (0.4409); Very rare (popmax 0.00695%, nfe).

How common is BDH2 p.Arg3Gln (c.8G>A) in the general population?

BDH2 p.Arg3Gln (c.8G>A) is very rare (popmax 0.00695%, nfe) (gnomAD).

What do computational predictors say about BDH2 p.Arg3Gln (c.8G>A)?

AlphaMissense predicts ambiguous (score 0.4409) — an in-silico prediction, not a clinical call.

BDH2 p.Arg3Gln

c.8G>A · rs769596421 · VCV2508412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4409 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4409	ambiguous
REVEL	0.468	indeterminate
SaProt	LLR -13.25	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 0.0025 · regional, not allelic
Overall
CADD	29.7	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 0.00695% European (non-Finnish) · 82/1,179,652 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00564% 91/1,613,494 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,386
African / African-American	0.00534%	18,725
Remaining individualsnot grpmax-eligible	0.0032%	31,228
East Asian	0.00223%	44,890
Admixed American	0.00167%	59,994
Finnishnot grpmax-eligible	0.00156%	63,994

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.Arg3Gln
Coding: c.8G>A
MANE Select: NM_020139
dbSNP: rs769596421
Type: single nucleotide variant
Location: chr4:103096247 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 1 PDB
Residue 3: a turn

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.Arg55Cys Uncertain significance ★ ⚠ same type
BDH2 p.Arg55His Uncertain significance ★ ⚠ same type
BDH2 p.Asn103His 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-arg3gln (accessed [today's date]).

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