Is TPK1 p.Phe101= (c.303T>C) pathogenic?

TPK1 p.Phe101= (c.303T>C) is classified Likely benign in TPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). Absent from gnomAD v4.1; Associated with childhood encephalopathy due to thiamine pyrophosphokinase deficiency.

What condition is associated with TPK1 p.Phe101= (c.303T>C)?

TPK1 p.Phe101= (c.303T>C) is associated with childhood encephalopathy due to thiamine pyrophosphokinase deficiency (ClinVar).

How common is TPK1 p.Phe101= (c.303T>C) in the general population?

TPK1 p.Phe101= (c.303T>C) is absent from gnomAD v4.1 (gnomAD).

TPK1 p.Phe101=

Q: How is Childhood encephalopathy due to thiamine pyrophosphokinase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.303T>C · rs2548093938 · VCV2789791

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

childhood encephalopathy due to thiamine pyrophosphokinase 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 0.08	GERP -4.2, phastCons 0.19
Overall
CADD	4.891	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TPK1
Protein: p.Phe101=
Coding: c.303T>C
MANE Select: NM_022445
dbSNP: rs2548093938
Type: single nucleotide variant
Location: chr7:144623217 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.92 · 2 PDB
Residue 101: an α-helix

Full TPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

childhood encephalopathy due to thiamine pyrophosphokinase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Childhood encephalopathy due to thiamine pyrophosphokinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TPK1 c.115+1G>T Likely pathogenic ★★ same condition
TPK1 c.185+1G>A Pathogenic/Likely pathogenic ★★ same condition
TPK1 c.44-2A>G Pathogenic/Likely pathogenic ★★ same condition
TPK1 c.501+4A>T Pathogenic ★★ same condition
TPK1 p.Asp222His Pathogenic/Likely pathogenic ★★ same condition
TPK1 p.Leu142Phe Pathogenic ★★ same condition
TPK1 p.Tyr82Ter Pathogenic/Likely pathogenic ★★ same condition
TPK1 p.Ala43Thr 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/tpk1-p-phe101 (accessed [today's date]).

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