Is PDHA1 p.Arg45fs (c.133delinsATTTCTGGG) pathogenic?

PDHA1 p.Arg45fs (c.133delinsATTTCTGGG) is classified Likely pathogenic in PDHA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). No gnomAD frequency available for this variant; Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Arg45fs (c.133delinsATTTCTGGG)?

PDHA1 p.Arg45fs (c.133delinsATTTCTGGG) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Arg45fs (c.133delinsATTTCTGGG) in the general population?

PDHA1 p.Arg45fs (c.133delinsATTTCTGGG) is no gnomAD frequency available for this variant (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.Arg45fs

c.133delinsATTTCTGGG · rs2519339591 · VCV3075682

Likely pathogenic Single submitter

Classification

Likely 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	predicted	premature termination codon in exon 3 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP 1.1, 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.Arg45fs
Coding: c.133delinsATTTCTGGG
MANE Select: NM_000284
dbSNP: rs2519339591
Type: Indel
Location: chrX:19349952 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 9 PDB
Residue 45: a β-strand

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.Arg45Trp Uncertain significance ★★ ⚠ same residue
PDHA1 p.Arg45Gln Likely benign ★★ same residue
PDHA1 p.Arg45= Likely benign ★ same residue
PDHA1 p.Arg45Gly Uncertain significance ★ same residue
PDHA1 p.Pro110fs Pathogenic same condition
PDHA1 p.Tyr65Gln Pathogenic same condition
PDHA1 p.Ala169Val Pathogenic ★★★ same condition
PDHA1 p.Arg304Ter 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-arg45fs (accessed [today's date]).

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