Is PDHA1 p.Ser152= (c.456G>A) pathogenic?

PDHA1 p.Ser152= (c.456G>A) is classified Likely benign in PDHA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-02). Very rare (popmax 0.00346%, afr); Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Ser152= (c.456G>A)?

PDHA1 p.Ser152= (c.456G>A) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Ser152= (c.456G>A) in the general population?

PDHA1 p.Ser152= (c.456G>A) is very rare (popmax 0.00346%, afr) (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.Ser152=

c.456G>A · rs1358837850 · VCV512149

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00346%, afr)

Conditions

pyruvate dehydrogenase E1-alpha deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -8.1	GERP -3.9
Overall
CADD	0.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00346% African / African-American · 2/57,772 alleles

Filtering AF 0.000574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.000248% 3/1,210,381 alleles · very rare exomes 3/1,096,691 · genomes 0/113,690 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00346%	28,886
Remaining individualsnot grpmax-eligible	0.0021%	47,616

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.Ser152=
Coding: c.456G>A
MANE Select: NM_000284
dbSNP: rs1358837850
Type: single nucleotide variant
Location: chrX:19353119 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 9 PDB
Residue 152: 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.Ser152Leu Likely pathogenic ★★ same residue
PDHA1 p.Ser152Pro Likely pathogenic same residue
PDHA1 p.Ser152Thr Likely pathogenic 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

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-ser152 (accessed [today's date]).

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