Is PDHA1 p.Arg288fs (c.861_862insT) pathogenic?

PDHA1 p.Arg288fs (c.861862insT) is classified Pathogenic in PDHA1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-10-15). No gnomAD frequency available for this variant; Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Arg288fs (c.861_862insT)?

PDHA1 p.Arg288fs (c.861_862insT) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Arg288fs (c.861_862insT) in the general population?

PDHA1 p.Arg288fs (c.861_862insT) 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.Arg288fs

c.861_862insT · rs606231190 · VCV10886

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

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 9 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.004	GERP 0.13, phastCons 0.82

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.Arg288fs
Coding: c.861_862insT
MANE Select: NM_000284
dbSNP: rs606231190
Type: Insertion
Location: chrX:19357681 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 9 PDB
Residue 288: a UniProt-annotated variant site (in pdhad)

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.Arg288Cys Pathogenic/Likely pathogenic ★★ same residue
PDHA1 p.Arg288His Pathogenic ★★ same residue
PDHA1 p.Arg288Leu Likely pathogenic same residue
PDHA1 p.Arg288Ser Pathogenic same residue
PDHA1 p.Asp356fs Pathogenic same condition
PDHA1 p.Glu305_Glu306insIleValThrValHisGluLys Likely pathogenic same condition
PDHA1 p.Leu5fs Pathogenic same condition
PDHA1 p.Met282delinsIleLeu 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/pdha1-p-arg288fs (accessed [today's date]).

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