Is CLK2 p.Ser37Asn (c.110G>A) pathogenic?

CLK2 p.Ser37Asn (c.110G>A) is classified Uncertain significance in CLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.3192); Very rare (popmax 0.00446%, eas).

How common is CLK2 p.Ser37Asn (c.110G>A) in the general population?

CLK2 p.Ser37Asn (c.110G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CLK2 p.Ser37Asn (c.110G>A)?

AlphaMissense predicts likely benign (score 0.3192) — an in-silico prediction, not a clinical call.

CLK2 p.Ser37Asn

c.110G>A · rs566634888 · VCV2542936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3192	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -9.19	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 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,209 bp · p 0.98 · regional, not allelic
Overall
CADD	22.5	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 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00041% 6/1,461,868 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.000169%	590,019

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.Ser37Asn
Coding: c.110G>A
MANE Select: NM_001294338
dbSNP: rs566634888
Type: single nucleotide variant
Location: chr1:155270868 (GRCh38)
Gene constraint: LOEUF 0.273 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.61 · 6 PDB
Residue 37: the 'disordered' region

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

Similar variants

CLK2 p.Ser37Gly 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
CLK2 p.Arg115Gln 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-ser37asn (accessed [today's date]).

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