Is TYMS p.Glu150Asp (c.450A>T) pathogenic?

TYMS p.Glu150Asp (c.450A>T) is classified Likely benign in TYMS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0759); Ultra-rare (popmax 0.0126%, nfe).

How common is TYMS p.Glu150Asp (c.450A>T) in the general population?

TYMS p.Glu150Asp (c.450A>T) is ultra-rare (popmax 0.0126%, nfe) (gnomAD).

What do computational predictors say about TYMS p.Glu150Asp (c.450A>T)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

TYMS p.Glu150Asp

c.450A>T · VCV4194481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -4.16	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 0.24	GERP -1.8, phastCons 0.99
Regional constraint	o/e 0.70	unconstrained · MANE · 14 kb · p 5.6e-08 · regional, not allelic
Overall
CADD	14.03	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% European (non-Finnish) · 148/1,178,638 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.00944% 152/1,609,448 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0126%	7,964
Remaining individualsnot grpmax-eligible	0.00321%	31,105
African / African-American	0.00268%	37,265

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.Glu150Asp
Coding: c.450A>T
MANE Select: NM_001071
Type: single nucleotide variant
Location: chr18:662316 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.05 · 61 PDB
Residue 150: a UniProt-annotated variant site (in dkcd; reduced tyms levels in patient cells); a β-strand

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-glu150asp (accessed [today's date]).

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