Is TK1 p.Arg70Trp (c.208C>T) pathogenic?

TK1 p.Arg70Trp (c.208C>T) is classified Uncertain significance in TK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.2612); Very rare (popmax 0.00891%, eas).

How common is TK1 p.Arg70Trp (c.208C>T) in the general population?

TK1 p.Arg70Trp (c.208C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about TK1 p.Arg70Trp (c.208C>T)?

AlphaMissense predicts likely benign (score 0.2612) — an in-silico prediction, not a clinical call.

TK1 p.Arg70Trp

c.208C>T · VCV3326241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2612 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2612	likely benign
REVEL	0.597	indeterminate
SaProt	LLR -11.83	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 12 kb · p 0.00027 · regional, not allelic
Overall
CADD	32.0	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 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00279% 45/1,612,514 alleles · very rare exomes 41/1,461,282 · genomes 4/151,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.00641%	15,605
African / African-American	0.00536%	18,640
Admixed American	0.00502%	19,911
European (non-Finnish)	0.00237%	42,123
South Asian	0.0022%	45,496

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.Arg70Trp
Coding: c.208C>T
MANE Select: NM_003258
Type: single nucleotide variant
Location: chr17:78185056 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.72 · 4 PDB
Residue 70: 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.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-arg70trp (accessed [today's date]).

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