Is PDHB p.Ser159= (c.477A>C) pathogenic?

PDHB p.Ser159= (c.477A>C) is classified Likely benign in PDHB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-31). Ultra-rare (popmax 0.0187%, afr); Associated with pyruvate dehydrogenase E1-beta deficiency.

What condition is associated with PDHB p.Ser159= (c.477A>C)?

PDHB p.Ser159= (c.477A>C) is associated with pyruvate dehydrogenase E1-beta deficiency, pyruvate dehydrogenase deficiency (ClinVar).

How common is PDHB p.Ser159= (c.477A>C) in the general population?

PDHB p.Ser159= (c.477A>C) is ultra-rare (popmax 0.0187%, afr) (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.Ser159=

c.477A>C · rs569429778 · VCV991901

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

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 -1.2	GERP -4.6, phastCons 0.002
Overall
CADD	7.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/75,058 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.00136% 22/1,613,922 alleles · ultra-rare exomes 10/1,461,572 · genomes 12/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,361
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.005%	20,009
European (non-Finnish)	8.48e-05%	1,179,748

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.Ser159=
Coding: c.477A>C
MANE Select: NM_000925
dbSNP: rs569429778
Type: single nucleotide variant
Location: chr3:58430769 (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

Also linked: pyruvate dehydrogenase deficiency

For Pyruvate dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive, Not applicable, X-linked dominant
Onset: Childhood, Infancy, Neonatal

Similar variants

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
PDHB p.Arg71Gln Uncertain significance ★★ same condition
PDHB p.Asn194Lys 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-ser159 (accessed [today's date]).

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