Is CSNK1D p.Pro342Ala (c.1024C>G) pathogenic?

CSNK1D p.Pro342Ala (c.1024C>G) is classified Uncertain significance in CSNK1D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0484); Ultra-rare (popmax 0.0121%, nfe).

How common is CSNK1D p.Pro342Ala (c.1024C>G) in the general population?

CSNK1D p.Pro342Ala (c.1024C>G) is ultra-rare (popmax 0.0121%, nfe) (gnomAD).

What do computational predictors say about CSNK1D p.Pro342Ala (c.1024C>G)?

AlphaMissense predicts likely benign (score 0.0484) — an in-silico prediction, not a clinical call.

CSNK1D p.Pro342Ala

c.1024C>G · rs906917946 · VCV3078271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0484 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0484	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.55	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 9.5	GERP 0.41, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,640 bp · p 0.061 · regional, not allelic
Overall
CADD	19.63	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 0.0121% European (non-Finnish) · 139/1,146,580 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00984%

Overall 0.00935% 144/1,540,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0121%	8,249
Admixed American	0.00393%	25,477
African / African-American	0.00274%	36,514
Remaining individualsnot grpmax-eligible	0.00167%	59,952

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.Pro342Ala
Coding: c.1024C>G
MANE Select: NM_001893
dbSNP: rs906917946
Type: single nucleotide variant
Location: chr17:82249464 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 82.10 · 53 PDB
Residue 342: the 'centrosomal localization signal (cls)' region; the 'disordered' region; the 'autoinhibitory' 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-pro342ala (accessed [today's date]).

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