Is CLK2 p.Arg483Gln (c.1448G>A) pathogenic?

CLK2 p.Arg483Gln (c.1448G>A) is classified Uncertain significance in CLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0706); Very rare (popmax 0.01%, amr).

How common is CLK2 p.Arg483Gln (c.1448G>A) in the general population?

CLK2 p.Arg483Gln (c.1448G>A) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CLK2 p.Arg483Gln (c.1448G>A)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

CLK2 p.Arg483Gln

c.1448G>A · VCV4003727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,041 bp · p 0.32 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,028 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000958% 14/1,461,730 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,005
South Asian	0.00329%	30,361
African / African-American	0.00133%	75,060
European (non-Finnish)	0.000339%	295,006

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.Arg483Gln
Coding: c.1448G>A
MANE Select: NM_001294338
Type: single nucleotide variant
Location: chr1:155263270 (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.Arg483Gly Uncertain significance ★ ⚠ same residue
CLK2 p.Arg483Trp 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-arg483gln (accessed [today's date]).

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