Is TYMS p.Ser120Arg (c.360C>G) pathogenic?

TYMS p.Ser120Arg (c.360C>G) is classified Uncertain significance in TYMS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.179); Very rare (popmax 0.00223%, eas).

How common is TYMS p.Ser120Arg (c.360C>G) in the general population?

TYMS p.Ser120Arg (c.360C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about TYMS p.Ser120Arg (c.360C>G)?

AlphaMissense predicts likely benign (score 0.179) — an in-silico prediction, not a clinical call.

TYMS p.Ser120Arg

c.360C>G · rs773564286 · VCV2560095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.179	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -5.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 14 kb · p 5.6e-08 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,613,940 alleles · very rare exomes 6/1,461,752 · genomes 0/152,188 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
South Asian	0.0011%	91,058
European (non-Finnish)	0.000339%	294,992

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: TYMS
Protein: p.Ser120Arg
Coding: c.360C>G
MANE Select: NM_001071
dbSNP: rs773564286
Type: single nucleotide variant
Location: chr18:662226 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.05 · 61 PDB
Residue 120: a UniProt-annotated variant site (in dkcd; reduced tyms levels in patient cells); an α-helix

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

Similar variants

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
TYMS p.Pro24Thr 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-ser120arg (accessed [today's date]).

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