Is TK1 p.Leu89Pro (c.266T>C) pathogenic?

TK1 p.Leu89Pro (c.266T>C) is classified Uncertain significance in TK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.2618); No allele count reported in gnomAD v4.1 (AN 1,596,208).

How common is TK1 p.Leu89Pro (c.266T>C) in the general population?

TK1 p.Leu89Pro (c.266T>C) is no allele count reported in gnomAD v4.1 (AN 1,596,208) (gnomAD).

What do computational predictors say about TK1 p.Leu89Pro (c.266T>C)?

AlphaMissense predicts likely benign (score 0.2618) — an in-silico prediction, not a clinical call.

TK1 p.Leu89Pro

c.266T>C · VCV3969112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2618 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,208)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2618	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -11.44	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.5, phastCons 0.66
Regional constraint	o/e 0.80	unconstrained · MANE · 12 kb · p 0.00027 · regional, not allelic
Overall
CADD	23.9	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

No allele count reported in gnomAD v4.1 (AN 1,596,208). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TK1
Protein: p.Leu89Pro
Coding: c.266T>C
MANE Select: NM_003258
Type: single nucleotide variant
Location: chr17:78182626 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.72 · 4 PDB
Residue 89: an α-helix

Full TK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TK1 p.Ala198= Benign ★★ same type
TK1 p.Ala151Val Uncertain significance ★ ⚠ same type
TK1 p.Ala193Thr Uncertain significance ★ ⚠ same type
TK1 p.Arg186Trp Uncertain significance ★ ⚠ same type
TK1 p.Arg39Cys Uncertain significance ★ ⚠ same type
TK1 p.Arg41Cys Uncertain significance ★ ⚠ same type
TK1 p.Arg60His Uncertain significance ★ ⚠ same type
TK1 p.Arg70Trp 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/tk1-p-leu89pro (accessed [today's date]).

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