Is PDHA1 p.Asp348fs (c.1043_1053del) pathogenic?

PDHA1 p.Asp348fs (c.10431053del) is classified Pathogenic in PDHA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-03). Absent from gnomAD; Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Asp348fs (c.1043_1053del)?

PDHA1 p.Asp348fs (c.1043_1053del) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Asp348fs (c.1043_1053del) in the general population?

PDHA1 p.Asp348fs (c.1043_1053del) is absent from gnomAD (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.Asp348fs

c.1043_1053del · rs2518507652 · VCV2121087

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 0.081, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDHA1
Protein: p.Asp348fs
Coding: c.1043_1053del
MANE Select: NM_000284
dbSNP: rs2518507652
Type: Deletion
Location: chrX:19359522 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 9 PDB
Residue 348: an α-helix

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.Asp348_Gln351del Uncertain significance ★ same residue
PDHA1 c.1009-16_1010del Pathogenic/Likely pathogenic ★★ same condition
PDHA1 c.1011_1034del Pathogenic/Likely pathogenic ★★ same condition
PDHA1 p.Asp348Val Uncertain significance ★★ ⚠ same residue
PDHA1 c.1008+1_1008+27del Pathogenic ★ same condition
PDHA1 p.Arg343fs Pathogenic ★ same condition
PDHA1 p.Arg378fs Pathogenic ★ same condition
PDHA1 p.Gly230fs 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-asp348fs (accessed [today's date]).

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