Is CSNK1D p.Pro348Arg (c.1043C>G) pathogenic?

CSNK1D p.Pro348Arg (c.1043C>G) is classified Uncertain significance in CSNK1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.146); Very rare (popmax 8.73e-05%, nfe).

How common is CSNK1D p.Pro348Arg (c.1043C>G) in the general population?

CSNK1D p.Pro348Arg (c.1043C>G) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

What do computational predictors say about CSNK1D p.Pro348Arg (c.1043C>G)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

CSNK1D p.Pro348Arg

c.1043C>G · VCV3497824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -5.93	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,640 bp · p 0.061 · regional, not allelic
Overall
CADD	23.3	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 8.73e-05% European (non-Finnish) · 1/1,146,088 alleles

Overall 7.22e-05% 1/1,385,816 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: CSNK1D
Protein: p.Pro348Arg
Coding: c.1043C>G
MANE Select: NM_001893
Type: single nucleotide variant
Location: chr17:82249445 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 82.10 · 53 PDB
Residue 348: the 'centrosomal localization signal (cls)' region; the 'disordered' region

Full CSNK1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSNK1D p.Ala304= Benign ★★ same type
CSNK1D p.Cys71= Benign/Likely benign ★★ same type
CSNK1D p.Ala30Val Uncertain significance ★ ⚠ same type
CSNK1D p.Ala36Thr Uncertain significance ★ same type
CSNK1D p.Arg306Trp Uncertain significance ★ ⚠ same type
CSNK1D p.Arg311Gln Uncertain significance ★ ⚠ same type
CSNK1D p.Arg314Gln Uncertain significance ★ ⚠ same type
CSNK1D p.Arg324Cys 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/csnk1d-p-pro348arg (accessed [today's date]).

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