Is TYMP p.Val185fs (c.554_561del) pathogenic?

TYMP p.Val185fs (c.554561del) is classified Likely pathogenic in TYMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). No gnomAD frequency available for this variant; Associated with mitochondrial DNA depletion syndrome 1.

What condition is associated with TYMP p.Val185fs (c.554_561del)?

TYMP p.Val185fs (c.554_561del) is associated with mitochondrial DNA depletion syndrome 1 (ClinVar).

How common is TYMP p.Val185fs (c.554_561del) in the general population?

TYMP p.Val185fs (c.554_561del) is no gnomAD frequency available for this variant (gnomAD).

TYMP p.Val185fs

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.554_561del · rs2522530917 · VCV3240673

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

mitochondrial DNA depletion syndrome 1

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 2.2	GERP -0.23, phastCons 1

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.Val185fs
Coding: c.554_561del
MANE Select: NM_001953
dbSNP: rs2522530917
Type: Deletion
Location: chr22:50527673 (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 185: a β-strand

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

Disease context

mitochondrial DNA depletion syndrome 1 — 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.Val185Glu Uncertain significance ★ ⚠ same residue
TYMP p.Ala3_Leu4insTer Pathogenic/Likely pathogenic ★★ same condition
TYMP c.207_214+6del Likely pathogenic ★ same condition
TYMP p.Leu255del Pathogenic ★ same condition
TYMP p.Thr9fs Likely pathogenic ★ same condition
TYMP p.Val232fs Likely pathogenic ★ same condition
TYMP p.Ser261_Leu262insTer Pathogenic same condition
TYMP p.Val241fs 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-val185fs (accessed [today's date]).

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