Is CCNK p.Met1Val (c.1A>G) pathogenic?

CCNK p.Met1Val (c.1A>G) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-12). Absent from gnomAD v4.1; Associated with intellectual developmental disorder with hypertelorism and distinctive facies.

How common is CCNK p.Met1Val (c.1A>G) in the general population?

CCNK p.Met1Val (c.1A>G) is absent from gnomAD v4.1 (gnomAD).

CCNK p.Met1Val

Q: What condition is associated with CCNK p.Met1Val (c.1A>G)?

CCNK p.Met1Val (c.1A>G) is associated with intellectual developmental disorder with hypertelorism and distinctive facies (ClinVar).

c.1A>G · rs2504012729 · VCV1708081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual developmental disorder with hypertelorism and distinctive facies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.391	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCNK
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_001099402
dbSNP: rs2504012729
Type: single nucleotide variant
Location: chr14:99492678 (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

Disease context

intellectual developmental disorder with hypertelorism and distinctive facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCNK p.Arg80Cys Uncertain significance ★★ ⚠ same condition
CCNK p.Val246Ile Uncertain significance ★★ ⚠ same condition
CCNK c.280-5T>C Benign ★★ same condition
CCNK p.Lys111Glu Likely pathogenic ★ same condition
CCNK p.Glu46fs Uncertain significance ★ same condition
CCNK p.Arg48Gln Uncertain significance ★★ ⚠ same type
CCNK p.Ser11= Likely benign ★★ same type
CCNK p.Ala54Thr 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-met1val (accessed [today's date]).

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