Is PDHA1 p.Pro110fs (c.328delinsAGA) pathogenic?

PDHA1 p.Pro110fs (c.328delinsAGA) is classified Pathogenic in PDHA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-10-15). Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Pro110fs (c.328delinsAGA)?

PDHA1 p.Pro110fs (c.328delinsAGA) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How is Pyruvate dehydrogenase deficiency inherited?

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

PDHA1 p.Pro110fs

c.328delinsAGA · VCV4070496

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

pyruvate dehydrogenase E1-alpha deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PDHA1
Protein: p.Pro110fs
Coding: c.328delinsAGA
MANE Select: NM_000284
Type: Indel
Location: chrX:19351317 (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.Pro110= Likely benign ★ same residue
PDHA1 p.Pro110His Pathogenic ⚠ same residue
PDHA1 p.Arg45fs Likely pathogenic ★ same condition
PDHA1 p.Pro110Ala Uncertain significance ★ ⚠ same residue
PDHA1 p.Tyr65Gln Pathogenic same condition
PDHA1 p.Ala169Val Pathogenic ★★★ same condition
PDHA1 p.Arg304Ter Pathogenic ★★★ same condition
PDHA1 p.Arg378Cys 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/pdha1-p-pro110fs (accessed [today's date]).

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