Is TYMP p.Phe236Ser (c.707T>C) pathogenic?

TYMP p.Phe236Ser (c.707T>C) is classified Pathogenic in TYMP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-01-14). AlphaMissense: likely pathogenic (0.637); Absent from gnomAD v4.1; Associated with mitochondrial DNA depletion syndrome 1.

What condition is associated with TYMP p.Phe236Ser (c.707T>C)?

TYMP p.Phe236Ser (c.707T>C) is associated with mitochondrial DNA depletion syndrome 1 (ClinVar).

How common is TYMP p.Phe236Ser (c.707T>C) in the general population?

TYMP p.Phe236Ser (c.707T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TYMP p.Phe236Ser (c.707T>C)?

AlphaMissense predicts likely pathogenic (score 0.637) — an in-silico prediction, not a clinical call.

TYMP p.Phe236Ser

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.707T>C · rs1064792868 · VCV223038

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.637 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial DNA depletion syndrome 1

Computational evidence

Protein change
AlphaMissense	0.637	likely pathogenic ✓ concordant with ClinVar
REVEL	0.705	pathogenic-leaning
SaProt	LLR -10.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.4, phastCons 0.33
Regional constraint	o/e 1.24	unconstrained · MANE · 3,936 bp · p 9.1e-10 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Phe236Ser
Coding: c.707T>C
MANE Select: NM_001953
dbSNP: rs1064792868
Type: single nucleotide variant
Location: chr22:50527223 (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 236: 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.Phe236= Likely benign ★ same residue
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

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-phe236ser (accessed [today's date]).

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