Is TK1 p.Ala198= (c.594C>T) pathogenic?

TK1 p.Ala198= (c.594C>T) is classified Benign in TK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-05). Common (popmax 8.15%, afr) — too common for a highly-penetrant pathogenic allele.

TK1 p.Ala198=

Q: How common is TK1 p.Ala198= (c.594C>T) in the general population?

TK1 p.Ala198= (c.594C>T) is common (popmax 8.15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.594C>T · rs1065767 · VCV785585

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.15%, afr) — too common for a highly-penetrant pathogenic allele

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 -6.5	GERP -3.4
Overall
CADD	1.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.15% African / African-American · 6,117/75,042 alleles

Filtering AF 7.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.91%

Overall 0.421% 6,802/1,613,828 alleles · common exomes 3,344/1,461,494 · genomes 3,458/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.15%	12
Remaining individualsnot grpmax-eligible	0.514%	195
Admixed American	0.427%	234
Middle Eastern	0.38%	263
South Asian	0.0242%	4,138
European (non-Finnish)	0.00534%	18,728

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: TK1
Protein: p.Ala198=
Coding: c.594C>T
MANE Select: NM_003258
dbSNP: rs1065767
Type: single nucleotide variant
Location: chr17:78174870 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.72 · 4 PDB

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

Similar variants

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
TK1 p.Arg82Gln 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-ala198 (accessed [today's date]).

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