Is CCNK p.Ser11= (c.33A>G) pathogenic?

CCNK p.Ser11= (c.33A>G) is classified Likely benign in CCNK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-13). Ultra-rare (popmax 0.0817%, amr).

How common is CCNK p.Ser11= (c.33A>G) in the general population?

CCNK p.Ser11= (c.33A>G) is ultra-rare (popmax 0.0817%, amr) (gnomAD).

CCNK p.Ser11=

c.33A>G · rs2069484 · VCV2644506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0817%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.8	GERP 1.9, phastCons 1
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0817% Admixed American · 48/58,780 alleles

Filtering AF 0.0641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0625%

Overall 0.0594% 957/1,610,292 alleles · ultra-rare exomes 871/1,457,938 · genomes 86/152,354 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0828%	1,207
Admixed Americangrpmax	0.0817%	1,225
European (non-Finnish)	0.068%	1,470
Remaining individualsnot grpmax-eligible	0.0513%	1,948
African / African-American	0.0281%	3,558
South Asian	0.00111%	90,270

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCNK
Protein: p.Ser11=
Coding: c.33A>G
MANE Select: NM_001099402
dbSNP: rs2069484
Type: single nucleotide variant
Location: chr14:99492710 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.43 · 43 PDB

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

Similar variants

CCNK p.Arg48Gln Uncertain significance ★★ ⚠ same type
CCNK p.Arg80Cys Uncertain significance ★★ ⚠ same type
CCNK p.Val246Ile Uncertain significance ★★ ⚠ same type
CCNK c.280-5T>C Benign ★★ same type
CCNK p.Lys111Glu Likely pathogenic ★ same type
CCNK p.Ala54Thr Uncertain significance ★ ⚠ same type
CCNK p.Arg121Cys Uncertain significance ★ ⚠ same type
CCNK p.Arg51Ter 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/ccnk-p-ser11 (accessed [today's date]).

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