Is PDHA1 p.Val23= (c.69G>A) pathogenic?

PDHA1 p.Val23= (c.69G>A) is classified Benign/Likely benign in PDHA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-11). Very rare (popmax 0.00668%, nfe); Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Val23= (c.69G>A)?

PDHA1 p.Val23= (c.69G>A) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Val23= (c.69G>A) in the general population?

PDHA1 p.Val23= (c.69G>A) is very rare (popmax 0.00668%, nfe) (gnomAD).

How is Pyruvate dehydrogenase deficiency inherited?

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

PDHA1 p.Val23=

c.69G>A · rs770667770 · VCV914927

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, nfe)

Conditions

pyruvate dehydrogenase E1-alpha deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -0.052, phastCons 1
Overall
CADD	6.937	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% European (non-Finnish) · 58/868,038 alleles

Filtering AF 0.00524% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00479%

Overall 0.005% 59/1,180,080 alleles · very rare exomes 55/1,067,730 · genomes 4/112,350 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00668%	14,966
African / African-American	0.00176%	56,823

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: PDHA1
Protein: p.Val23=
Coding: c.69G>A
MANE Select: NM_000284
dbSNP: rs770667770
Type: single nucleotide variant
Location: chrX:19349323 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 9 PDB

Full PDHA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pyruvate dehydrogenase E1-alpha 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

PDHA1 p.Val23Met Uncertain significance ★ ⚠ same residue
PDHA1 p.Ala169Val Pathogenic ★★★ same condition
PDHA1 p.Arg304Ter Pathogenic ★★★ same condition
PDHA1 p.Arg378Cys Pathogenic ★★★ ⚠ same condition
PDHA1 p.Arg72Cys Likely pathogenic ★★★ same condition
PDHA1 p.Ile280Ser Uncertain significance ★★★ ⚠ same condition
PDHA1 p.Ala265= Benign ★★★ same condition
PDHA1 p.Glu333Asp Benign ★★★ 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/pdha1-p-val23 (accessed [today's date]).

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