Is TYMP p.Ala252= (c.756A>C) pathogenic?

TYMP p.Ala252= (c.756A>C) is classified Conflicting classifications of pathogenicity in TYMP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-08-31). Absent from gnomAD v4.1; Associated with mitochondrial DNA depletion syndrome 1.

What condition is associated with TYMP p.Ala252= (c.756A>C)?

TYMP p.Ala252= (c.756A>C) is associated with mitochondrial DNA depletion syndrome 1 (ClinVar).

How common is TYMP p.Ala252= (c.756A>C) in the general population?

TYMP p.Ala252= (c.756A>C) is absent from gnomAD v4.1 (gnomAD).

TYMP p.Ala252=

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.756A>C · rs886057635 · VCV342147

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

mitochondrial DNA depletion syndrome 1

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 -4.5	GERP -4
Overall
CADD	0.689	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: TYMP
Protein: p.Ala252=
Coding: c.756A>C
MANE Select: NM_001953
dbSNP: rs886057635
Type: single nucleotide variant
Location: chr22:50527174 (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 252: an α-helix

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 c.1301-1G>A Likely pathogenic ★★ same condition
TYMP c.214+1G>T Likely pathogenic ★★ same condition
TYMP c.417+1G>A Pathogenic ★★ same condition
TYMP c.418-1G>A Likely pathogenic ★★ same condition
TYMP c.646+1G>A Pathogenic/Likely pathogenic ★★ same condition
TYMP c.647-1G>A Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Ala216Val Likely pathogenic ★★ same condition
TYMP p.Asp114Asn 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-ala252 (accessed [today's date]).

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