Is TYMP p.Pro414= (c.1242G>A) pathogenic?

TYMP p.Pro414= (c.1242G>A) is classified Likely benign in TYMP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0389%, nfe); Associated with mitochondrial neurogastrointestinal encephalomyopathy.

What condition is associated with TYMP p.Pro414= (c.1242G>A)?

TYMP p.Pro414= (c.1242G>A) is associated with mitochondrial neurogastrointestinal encephalomyopathy (ClinVar).

How common is TYMP p.Pro414= (c.1242G>A) in the general population?

TYMP p.Pro414= (c.1242G>A) is ultra-rare (popmax 0.0389%, nfe) (gnomAD).

TYMP p.Pro414=

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.1242G>A · rs1013301590 · VCV764487

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0389%, nfe)

Conditions

mitochondrial neurogastrointestinal encephalomyopathy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.33	GERP -1.1, phastCons 0.009
Overall
CADD	9.745	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0389% European (non-Finnish) · 437/1,124,162 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0346%

Overall 0.0315% 467/1,482,378 alleles · ultra-rare exomes 443/1,330,176 · genomes 24/152,202 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0389%	2,572
Remaining individualsnot grpmax-eligible	0.0244%	4,094
Finnishnot grpmax-eligible	0.0183%	5,450
African / African-American	0.00586%	17,065
Ashkenazi Jewishnot grpmax-eligible	0.00373%	26,838
South Asian	0.00254%	39,307
Admixed American	0.00229%	43,660

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TYMP
Protein: p.Pro414=
Coding: c.1242G>A
MANE Select: NM_001953
dbSNP: rs1013301590
Type: single nucleotide variant
Location: chr22:50526059 (GRCh38)

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)

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-pro414 (accessed [today's date]).

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