Is PDHB p.Ser5= (c.15T>C) pathogenic?

PDHB p.Ser5= (c.15T>C) is classified Likely benign in PDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). Very rare (popmax 0.00223%, eas); Associated with pyruvate dehydrogenase E1-beta deficiency.

What condition is associated with PDHB p.Ser5= (c.15T>C)?

PDHB p.Ser5= (c.15T>C) is associated with pyruvate dehydrogenase E1-beta deficiency (ClinVar).

How common is PDHB p.Ser5= (c.15T>C) in the general population?

PDHB p.Ser5= (c.15T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Pyruvate dehydrogenase deficiency inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PDHB p.Ser5=

c.15T>C · rs775907917 · VCV1080310

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

pyruvate dehydrogenase E1-beta 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 -0.63	GERP -5.5
Overall
CADD	7.965	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,816 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000993% 16/1,611,716 alleles · very rare exomes 14/1,459,520 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,816
European (non-Finnish)	0.00127%	78,634

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: PDHB
Protein: p.Ser5=
Coding: c.15T>C
MANE Select: NM_000925
dbSNP: rs775907917
Type: single nucleotide variant
Location: chr3:58433795 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 94.18 · 9 PDB

Full PDHB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pyruvate dehydrogenase E1-beta 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

PDHB p.Ser5Pro Uncertain significance ★★ ⚠ same residue
PDHB p.Ser5Tyr Uncertain significance ★ ⚠ same residue
PDHB c.934+1G>A Likely pathogenic ★★ same condition
PDHB p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
PDHB p.Gln118Ter Likely pathogenic ★★ same condition
PDHB p.Met101Val Pathogenic ★★ ⚠ same condition
PDHB p.Ala150Ser Uncertain significance ★★ ⚠ same condition
PDHB p.Ala314Val 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/pdhb-p-ser5 (accessed [today's date]).

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