Is CLK3 p.Arg71Pro (c.212G>C) pathogenic?

CLK3 p.Arg71Pro (c.212G>C) is classified Uncertain significance in CLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.2103); Very rare (popmax 0.00801%, afr).

How common is CLK3 p.Arg71Pro (c.212G>C) in the general population?

CLK3 p.Arg71Pro (c.212G>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CLK3 p.Arg71Pro (c.212G>C)?

AlphaMissense predicts likely benign (score 0.2103) — an in-silico prediction, not a clinical call.

CLK3 p.Arg71Pro

c.212G>C · rs756011168 · VCV3145888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2103 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
AlphaMissense	0.2103	likely benign
REVEL	0.322	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 976 bp · p 0.088 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R219P vs ClinVar R71P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,922 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,614,078 alleles · very rare

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.Arg71Pro
Coding: c.212G>C
MANE Select: NM_001130028
dbSNP: rs756011168
Type: single nucleotide variant
Location: chr15:74620068 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 22 PDB
Residue 71: the 'disordered' region

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

Similar variants

CLK3 p.Arg71Trp 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-arg71pro (accessed [today's date]).

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