Is TYMS p.Arg46= (c.136A>C) pathogenic?

TYMS p.Arg46= (c.136A>C) is classified Likely benign in TYMS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-29). Absent from gnomAD v4.1; Associated with TYMS-related disorder.

What condition is associated with TYMS p.Arg46= (c.136A>C)?

TYMS p.Arg46= (c.136A>C) is associated with TYMS-related disorder (ClinVar).

How common is TYMS p.Arg46= (c.136A>C) in the general population?

TYMS p.Arg46= (c.136A>C) is absent from gnomAD v4.1 (gnomAD).

TYMS p.Arg46=

c.136A>C · rs1376079761 · VCV3053632

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

TYMS-related disorder

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 -0.089	GERP -3.1
Overall
CADD	14.69	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: TYMS
Protein: p.Arg46=
Coding: c.136A>C
MANE Select: NM_001071
dbSNP: rs1376079761
Type: single nucleotide variant
Location: chr18:657878 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.05 · 61 PDB
Residue 46: a β-strand

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

Disease context

TYMS-related disorder

Similar variants

TYMS p.Glu127= Benign same condition
TYMS p.Arg115Ter Pathogenic ★ same type
TYMS p.Ala4Ser Uncertain significance ★ ⚠ same type
TYMS p.Asp148Glu Uncertain significance ★ ⚠ same type
TYMS p.Glu87Lys Uncertain significance ★ ⚠ same type
TYMS p.Gly29Arg Uncertain significance ★ ⚠ same type
TYMS p.Pro15Arg Uncertain significance ★ ⚠ same type
TYMS p.Pro15His Uncertain significance ★ ⚠ same type

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/tyms-p-arg46 (accessed [today's date]).

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