Is TYMP p.Val204fs (c.610dup) pathogenic?

TYMP p.Val204fs (c.610dup) is classified Likely pathogenic in TYMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Associated with mitochondrial neurogastrointestinal encephalomyopathy.

What condition is associated with TYMP p.Val204fs (c.610dup)?

TYMP p.Val204fs (c.610dup) is associated with mitochondrial neurogastrointestinal encephalomyopathy (ClinVar).

TYMP p.Val204fs

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.610dup · VCV4062472

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

mitochondrial neurogastrointestinal encephalomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP 1.6, phastCons 0.042

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: TYMP
Protein: p.Val204fs
Coding: c.610dup
MANE Select: NM_001953
Type: Duplication
Location: chr22:50527623 (GRCh38)
Gene constraint: LOEUF 1.518 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 4 PDB
Residue 204: an α-helix

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

Disease context

mitochondrial neurogastrointestinal encephalomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mitochondrial neurogastrointestinal encephalomyopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TYMP p.Ala297fs Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Cys183fs Likely pathogenic ★★ same condition
TYMP p.Val204= Likely benign ★ same residue
TYMP c.1301-1G>A Likely pathogenic ★★ same condition
TYMP c.418-1G>A Likely pathogenic ★★ same condition
TYMP p.Ala135fs Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Ala216Val Likely pathogenic ★★ same condition
TYMP p.Ala268fs Pathogenic/Likely pathogenic ★★ 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/tymp-p-val204fs (accessed [today's date]).

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