Is PDHB p.Phe299= (c.897T>C) pathogenic?

PDHB p.Phe299= (c.897T>C) is classified Likely benign in PDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-29). Ultra-rare (popmax 0.0245%, eas); Associated with pyruvate dehydrogenase E1-beta deficiency.

What condition is associated with PDHB p.Phe299= (c.897T>C)?

PDHB p.Phe299= (c.897T>C) is associated with pyruvate dehydrogenase E1-beta deficiency (ClinVar).

How common is PDHB p.Phe299= (c.897T>C) in the general population?

PDHB p.Phe299= (c.897T>C) is ultra-rare (popmax 0.0245%, 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.Phe299=

c.897T>C · rs145795547 · VCV1114834

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, 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	<0.2	all four deltas below 0.2 · A>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2	GERP 0.065, phastCons 1
Overall
CADD	14.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,896 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00112% 18/1,614,188 alleles · ultra-rare exomes 15/1,461,860 · genomes 3/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
Remaining individualsnot grpmax-eligible	0.0032%	31,253
Admixed American	0.00167%	60,028
European (non-Finnish)	0.000339%	295,003

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.Phe299=
Coding: c.897T>C
MANE Select: NM_000925
dbSNP: rs145795547
Type: single nucleotide variant
Location: chr3:58428510 (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 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-phe299 (accessed [today's date]).

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