Is PDHB p.Val8= (c.24G>A) pathogenic?

PDHB p.Val8= (c.24G>A) is classified Likely benign in PDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-20). Very rare (popmax 0.000678%, nfe); Associated with pyruvate dehydrogenase E1-beta deficiency.

What condition is associated with PDHB p.Val8= (c.24G>A)?

PDHB p.Val8= (c.24G>A) is associated with pyruvate dehydrogenase E1-beta deficiency (ClinVar).

How common is PDHB p.Val8= (c.24G>A) in the general population?

PDHB p.Val8= (c.24G>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

How is Pyruvate dehydrogenase deficiency inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PDHB p.Val8=

c.24G>A · rs776938446 · VCV794269

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

pyruvate dehydrogenase E1-beta deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.62	donor gain · deltas
Pangolin	Δ0.39	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.3	GERP -0.085, phastCons 0.98
Overall
CADD	19.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,566 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,612,050 alleles · very rare exomes 10/1,459,838 · genomes 2/152,212 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00634%	15,769
European (non-Finnish)grpmax	0.000678%	147,446

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PDHB
Protein: p.Val8=
Coding: c.24G>A
MANE Select: NM_000925
dbSNP: rs776938446
Type: single nucleotide variant
Location: chr3:58433786 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 94.18 · 9 PDB

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

Disease context

pyruvate dehydrogenase E1-beta deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pyruvate dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive, Not applicable, X-linked dominant
Onset: Childhood, Infancy, Neonatal

Similar variants

PDHB c.934+1G>A Likely pathogenic ★★ same condition
PDHB p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
PDHB p.Gln118Ter Likely pathogenic ★★ same condition
PDHB p.Met101Val Pathogenic ★★ ⚠ same condition
PDHB p.Ala150Ser Uncertain significance ★★ ⚠ same condition
PDHB p.Ala314Val Uncertain significance ★★ ⚠ same condition
PDHB p.Arg71Gln Uncertain significance ★★ same condition
PDHB p.Asn194Lys Uncertain significance ★★ ⚠ same condition

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/pdhb-p-val8 (accessed [today's date]).

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