Is TYMP p.Gln245= (c.735G>A) pathogenic?

TYMP p.Gln245= (c.735G>A) is classified Benign/Likely benign in TYMP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-29). Ultra-rare (popmax 0.077%, nfe); Associated with mitochondrial neurogastrointestinal encephalomyopathy.

What condition is associated with TYMP p.Gln245= (c.735G>A)?

TYMP p.Gln245= (c.735G>A) is associated with mitochondrial neurogastrointestinal encephalomyopathy (ClinVar).

How common is TYMP p.Gln245= (c.735G>A) in the general population?

TYMP p.Gln245= (c.735G>A) is ultra-rare (popmax 0.077%, nfe) (gnomAD).

TYMP p.Gln245=

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.735G>A · rs139223629 · VCV215321

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.077%, nfe)

Conditions

mitochondrial neurogastrointestinal encephalomyopathy

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 0.65	GERP -2.5, phastCons 0.003
Overall
CADD	11.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.077% European (non-Finnish) · 909/1,180,008 alleles

Filtering AF 0.0728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0712%

Overall 0.148% 2,390/1,613,444 alleles · ultra-rare exomes 2,075/1,461,110 · genomes 315/152,334 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.52%	66
Ashkenazi Jewishnot grpmax-eligible	1.18%	85
Remaining individualsnot grpmax-eligible	0.203%	492
European (non-Finnish)grpmax	0.077%	1,298
Middle Eastern	0.0669%	1,495
Admixed American	0.0283%	3,531
South Asian	0.0176%	5,692
African / African-American	0.00799%	12,510

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln245=
Coding: c.735G>A
MANE Select: NM_001953
dbSNP: rs139223629
Type: single nucleotide variant
Location: chr22:50527195 (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 245: an α-helix

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)

Similar variants

TYMP p.Gln245Ter Likely pathogenic ★ same residue
TYMP c.1301-1G>A Likely pathogenic ★★ same condition
TYMP c.418-1G>A Likely pathogenic ★★ same condition
TYMP p.Ala216Val Likely pathogenic ★★ same condition
TYMP p.Asp114Asn Likely pathogenic ★★ same condition
TYMP p.Glu21Ter Pathogenic/Likely pathogenic ★★ same condition
TYMP p.Glu289Ala Pathogenic ★★ same condition
TYMP p.Gly145Arg Pathogenic/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-gln245 (accessed [today's date]).

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