Is PDHA1 p.Ser130= (c.390C>T) pathogenic?

PDHA1 p.Ser130= (c.390C>T) is classified Benign in PDHA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). Very rare (popmax 0.00257%, nfe); Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Ser130= (c.390C>T)?

PDHA1 p.Ser130= (c.390C>T) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Ser130= (c.390C>T) in the general population?

PDHA1 p.Ser130= (c.390C>T) is very rare (popmax 0.00257%, nfe) (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.Ser130=

c.390C>T · rs756138817 · VCV1169557

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00257%, nfe)

Conditions

pyruvate dehydrogenase E1-alpha deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.9
Overall
CADD	2.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00257% European (non-Finnish) · 23/893,918 alleles

Filtering AF 0.00171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00223% 27/1,208,668 alleles · very rare exomes 24/1,096,345 · genomes 3/112,323 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00257%	38,866
Finnishnot grpmax-eligible	0.00214%	46,682
Remaining individualsnot grpmax-eligible	0.0021%	47,523
South Asian	0.00176%	56,703
African / African-American	0.00175%	57,274

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.Ser130=
Coding: c.390C>T
MANE Select: NM_000284
dbSNP: rs756138817
Type: single nucleotide variant
Location: chrX:19351379 (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.Ser130Cys Uncertain significance ⚠ 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
PDHA1 p.Ala265= Benign ★★★ same condition
PDHA1 p.Glu333Asp Benign ★★★ 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-ser130 (accessed [today's date]).

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