Is TYMS p.Val223= (c.669G>A) pathogenic?

TYMS p.Val223= (c.669G>A) is classified Likely benign in TYMS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). Rare (popmax 0.257%, afr).

How common is TYMS p.Val223= (c.669G>A) in the general population?

TYMS p.Val223= (c.669G>A) is rare (popmax 0.257%, afr) (gnomAD).

TYMS p.Val223=

c.669G>A · VCV3770695

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.257%, afr)

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 2.5	GERP -0.01, phastCons 1
Overall
CADD	8.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.257% African / African-American · 193/74,994 alleles

Filtering AF 0.228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.216%

Overall 0.0134% 216/1,614,090 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.257%	389
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Middle Eastern	0.0165%	6,062
Admixed American	0.01%	10,002
European (non-Finnish)	0.000169%	590,016

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.Val223=
Coding: c.669G>A
MANE Select: NM_017512 · reported on NM_001071
Type: single nucleotide variant
Location: chr18:670804 (GRCh38)

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

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-val223 (accessed [today's date]).

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