Is TYMP p.Cys183fs (c.532_548dup) pathogenic?

TYMP p.Cys183fs (c.532548dup) is classified Likely pathogenic in TYMP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-21). Absent from gnomAD; Associated with mitochondrial neurogastrointestinal encephalomyopathy.

How common is TYMP p.Cys183fs (c.532_548dup) in the general population?

TYMP p.Cys183fs (c.532_548dup) is absent from gnomAD (gnomAD).

TYMP p.Cys183fs

Q: What condition is associated with TYMP p.Cys183fs (c.532_548dup)?

TYMP p.Cys183fs (c.532_548dup) is associated with mitochondrial neurogastrointestinal encephalomyopathy, mitochondrial DNA depletion syndrome 1 (ClinVar).

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.532_548dup · rs2522531011 · VCV2679397

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -0.33	GERP -3.5

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TYMP
Protein: p.Cys183fs
Coding: c.532_548dup
MANE Select: NM_001953
dbSNP: rs2522531011
Type: Duplication
Location: chr22:50527685 (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 183: a β-strand

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

Also linked: mitochondrial DNA depletion syndrome 1

For Mitochondrial neurogastrointestinal encephalomyopathy (Orphanet):

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

Similar variants

TYMP p.Cys183Arg Uncertain significance ★ ⚠ same residue
TYMP p.Cys183Tyr Uncertain significance ⚠ same residue
TYMP p.Ala297fs Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Cys182fs Likely pathogenic ★ same condition
TYMP p.Leu277fs Likely pathogenic ★ same condition
TYMP p.Ser30fs Pathogenic ★ same condition
TYMP p.Val204fs Likely pathogenic ★ same condition
TYMP p.Lys34fs 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-cys183fs (accessed [today's date]).

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