Is TAOK2 p.Ala487Glu (c.1460C>A) pathogenic?

TAOK2 p.Ala487Glu (c.1460C>A) is classified Uncertain significance in TAOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-09). AlphaMissense: ambiguous (0.4419); Very rare (popmax 8.73e-05%, nfe).

How common is TAOK2 p.Ala487Glu (c.1460C>A) in the general population?

TAOK2 p.Ala487Glu (c.1460C>A) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

What do computational predictors say about TAOK2 p.Ala487Glu (c.1460C>A)?

AlphaMissense predicts ambiguous (score 0.4419) — an in-silico prediction, not a clinical call.

TAOK2 p.Ala487Glu

c.1460C>A · rs1286967853 · VCV2808469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4419 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4419	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -5.36	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP -0.62, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 1,793 bp · p 1.6e-06 · regional, not allelic
Overall
CADD	23.6	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 8.73e-05% European (non-Finnish) · 1/1,145,462 alleles

Overall 6.46e-05% 1/1,547,620 alleles · very rare exomes 1/1,395,264 · genomes 0/152,356 · joint denominator

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: TAOK2
Protein: p.Ala487Glu
Coding: c.1460C>A
MANE Select: NM_016151
dbSNP: rs1286967853
Type: single nucleotide variant
Location: chr16:29985250 (GRCh38)
Gene constraint: LOEUF 0.459 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.17

Full TAOK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TAOK2 p.Ala487= Likely benign ★ same residue
TAOK2 p.Ala1057Val Uncertain significance ★★ ⚠ same type
TAOK2 p.Ala1062Val Uncertain significance ★★ ⚠ same type
TAOK2 p.Ala1148Thr Uncertain significance ★★ ⚠ same type
TAOK2 p.Ala444Val Uncertain significance ★★ ⚠ same type
TAOK2 p.Ala733Val Uncertain significance ★★ ⚠ same type
TAOK2 p.Ala747Val Uncertain significance ★★ ⚠ same type
TAOK2 p.Ala761Val 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/taok2-p-ala487glu (accessed [today's date]).

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