Is PDHA1 p.Ser390= (c.1170T>C) pathogenic?

PDHA1 p.Ser390= (c.1170T>C) is classified Benign in PDHA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). Ultra-rare (popmax 0.0687%, afr); Associated with pyruvate dehydrogenase E1-alpha deficiency.

What condition is associated with PDHA1 p.Ser390= (c.1170T>C)?

PDHA1 p.Ser390= (c.1170T>C) is associated with pyruvate dehydrogenase E1-alpha deficiency (ClinVar).

How common is PDHA1 p.Ser390= (c.1170T>C) in the general population?

PDHA1 p.Ser390= (c.1170T>C) is ultra-rare (popmax 0.0687%, 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.Ser390=

c.1170T>C · rs369973813 · VCV1167381

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0687%, afr)

Conditions

pyruvate dehydrogenase E1-alpha deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.638	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.82 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.8	GERP 0.83, phastCons 1
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0687% African / African-American · 39/56,806 alleles

Filtering AF 0.0516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0457%

Overall 0.0039% 47/1,205,877 alleles · ultra-rare exomes 25/1,094,932 · genomes 22/110,945 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0687%	1,457
Admixed American	0.00879%	11,383
Remaining individualsnot grpmax-eligible	0.00632%	15,828
European (non-Finnish)	0.000112%	892,196

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.Ser390=
Coding: c.1170T>C
MANE Select: NM_000284
dbSNP: rs369973813
Type: single nucleotide variant
Location: chrX:19359650 (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.Ser390fs 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-ser390 (accessed [today's date]).

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