Is TK2 p.Asp101Asn (c.301G>A) pathogenic?

TK2 p.Asp101Asn (c.301G>A) is classified Likely benign in TK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). AlphaMissense: likely benign (0.123); Rare (popmax 0.234%, eas).

How common is TK2 p.Asp101Asn (c.301G>A) in the general population?

TK2 p.Asp101Asn (c.301G>A) is rare (popmax 0.234%, eas) (gnomAD).

What do computational predictors say about TK2 p.Asp101Asn (c.301G>A)?

AlphaMissense predicts likely benign (score 0.123) — an in-silico prediction, not a clinical call.

TK2 p.Asp101Asn

c.301G>A · rs148450491 · VCV1644188

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.123 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.234%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.123	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -10.33	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 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 38 kb · p 0.097 · regional, not allelic
Overall
CADD	22.2	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 0.234% East Asian · 105/44,884 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.00892% 144/1,614,130 alleles · rare exomes 126/1,461,868 · genomes 18/152,262 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.234%	427
South Asian	0.0165%	6,072
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00186%	53,637

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: TK2
Protein: p.Asp101Asn
Coding: c.301G>A
MANE Select: NM_004614
dbSNP: rs148450491
Type: single nucleotide variant
Location: chr16:66531454 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01

Full TK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TK2 p.Asp101Gly Uncertain significance ★★ ⚠ same residue
TK2 c.156+2T>C Pathogenic/Likely pathogenic ★★ same type
TK2 c.157-2A>G Pathogenic/Likely pathogenic ★★ same type
TK2 p.Ala139Thr Pathogenic/Likely pathogenic ★★ same type
TK2 p.Ala139Val Pathogenic/Likely pathogenic ★★ same type
TK2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ same type
TK2 p.Arg130Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
TK2 p.Arg130Trp Pathogenic/Likely pathogenic ★★ 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/tk2-p-asp101asn (accessed [today's date]).

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