Is CLK2 p.Arg483Trp (c.1447C>T) pathogenic?

CLK2 p.Arg483Trp (c.1447C>T) is classified Uncertain significance in CLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.1686); Ultra-rare (popmax 0.0306%, afr).

How common is CLK2 p.Arg483Trp (c.1447C>T) in the general population?

CLK2 p.Arg483Trp (c.1447C>T) is ultra-rare (popmax 0.0306%, afr) (gnomAD).

What do computational predictors say about CLK2 p.Arg483Trp (c.1447C>T)?

AlphaMissense predicts likely benign (score 0.1686) — an in-silico prediction, not a clinical call.

CLK2 p.Arg483Trp

c.1447C>T · rs200444017 · VCV3145871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0306%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1686	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -11.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,041 bp · p 0.32 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.0306% African / African-American · 23/75,066 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.00211% 34/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0306%	3,264
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.000763%	131,116

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: CLK2
Protein: p.Arg483Trp
Coding: c.1447C>T
MANE Select: NM_001294338
dbSNP: rs200444017
Type: single nucleotide variant
Location: chr1:155263271 (GRCh38)
Gene constraint: LOEUF 0.273 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.61 · 6 PDB
Residue 483: an α-helix

Full CLK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLK2 p.Arg483Gln Uncertain significance ★ ⚠ same residue
CLK2 p.Arg483Gly Uncertain significance ★ ⚠ same residue
CLK2 p.Ala140Pro Uncertain significance ★ ⚠ same type
CLK2 p.Ala188Val Uncertain significance ★ ⚠ same type
CLK2 p.Ala480Val Uncertain significance ★ ⚠ same type
CLK2 p.Arg103Gln Uncertain significance ★ ⚠ same type
CLK2 p.Arg109Cys Uncertain significance ★ ⚠ same type
CLK2 p.Arg112Cys 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/clk2-p-arg483trp (accessed [today's date]).

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