Is PDHB p.Val330= (c.990C>G) pathogenic?

PDHB p.Val330= (c.990C>G) is classified Uncertain significance in PDHB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-22). Absent from gnomAD v4.1; Associated with pyruvate dehydrogenase phosphatase deficiency.

What condition is associated with PDHB p.Val330= (c.990C>G)?

PDHB p.Val330= (c.990C>G) is associated with pyruvate dehydrogenase phosphatase deficiency (ClinVar).

How common is PDHB p.Val330= (c.990C>G) in the general population?

PDHB p.Val330= (c.990C>G) is absent from gnomAD v4.1 (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.Val330=

c.990C>G · VCV4059501

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pyruvate dehydrogenase phosphatase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.33, phastCons 1
Overall
CADD	8.262	PHRED · no single calibrated threshold — expert panels disagree

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: PDHB
Protein: p.Val330=
Coding: c.990C>G
MANE Select: NM_000925
Type: single nucleotide variant
Location: chr3:58428124 (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 phosphatase 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.Val261Ala Uncertain significance ★★ ⚠ same condition
PDHB c.934+1G>T Likely pathogenic ★ same condition
PDHB p.Arg192Gln Likely pathogenic ★ same condition
PDHB p.Lys188Ter Likely pathogenic ★ same condition
PDHB p.Met1Thr Likely pathogenic ★ 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-val330 (accessed [today's date]).

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