Is TYMP p.Arg55fs (c.163_164del) pathogenic?

TYMP p.Arg55fs (c.163164del) is classified Likely pathogenic in TYMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-21). Associated with mitochondrial neurogastrointestinal encephalomyopathy.

What condition is associated with TYMP p.Arg55fs (c.163_164del)?

TYMP p.Arg55fs (c.163_164del) is associated with mitochondrial neurogastrointestinal encephalomyopathy (ClinVar).

TYMP p.Arg55fs

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.163_164del · VCV4814986

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 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -0.35

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

Variant & gene context

Gene: TYMP
Protein: p.Arg55fs
Coding: c.163_164del
MANE Select: NM_001953
Type: Deletion
Location: chr22:50529546 (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 55: 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.Ala135fs Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Ala3_Leu4insTer Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Arg55Lys Uncertain significance ★★ ⚠ same residue
TYMP p.Gln24fs Likely pathogenic ★ same condition
TYMP p.Arg55Thr Uncertain significance ★ ⚠ same residue
TYMP p.Arg55= Likely benign ★ same residue
TYMP c.1301-1G>A Likely pathogenic ★★ same condition
TYMP c.418-1G>A 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-arg55fs (accessed [today's date]).

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