Is CLK3 p.Arg62Gln (c.185G>A) pathogenic?

CLK3 p.Arg62Gln (c.185G>A) is classified Uncertain significance in CLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1248); Very rare (popmax 0.00891%, eas).

How common is CLK3 p.Arg62Gln (c.185G>A) in the general population?

CLK3 p.Arg62Gln (c.185G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CLK3 p.Arg62Gln (c.185G>A)?

AlphaMissense predicts likely benign (score 0.1248) — an in-silico prediction, not a clinical call.

CLK3 p.Arg62Gln

c.185G>A · rs779166711 · VCV3145886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1248 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1248	likely benign
REVEL	0.099	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 976 bp · p 0.088 · regional, not allelic
Overall
CADD	24.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R210Q vs ClinVar R62Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

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

Overall 0.000684% 10/1,461,844 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
Remaining individualsnot grpmax-eligible	0.0032%	31,256
South Asian	0.0011%	91,090
European (non-Finnish)	0.000254%	393,343

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: CLK3
Protein: p.Arg62Gln
Coding: c.185G>A
MANE Select: NM_001130028
dbSNP: rs779166711
Type: single nucleotide variant
Location: chr15:74620041 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 22 PDB
Residue 62: the 'disordered' region

Full CLK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLK3 p.Arg62Trp Uncertain significance ★ ⚠ same residue
CLK3 p.Pro89Arg Uncertain significance ★★ ⚠ same type
CLK3 c.125G>A Uncertain significance ★ same type
CLK3 c.19C>T Uncertain significance ★ same type
CLK3 c.310C>T Uncertain significance ★ same type
CLK3 c.374T>G Uncertain significance ★ same type
CLK3 c.-1+1G>C Uncertain significance ★ same type
CLK3 c.-12G>C 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/clk3-p-arg62gln (accessed [today's date]).

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