Is CCND2 p.Lys270Ter (c.808A>T) pathogenic?

CCND2 p.Lys270Ter (c.808A>T) is classified Pathogenic in CCND2 (ClinVar, Single submitter, 3 submitters; last evaluated 2023-07-16). Absent from gnomAD v4.1; Associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3.

What condition is associated with CCND2 p.Lys270Ter (c.808A>T)?

CCND2 p.Lys270Ter (c.808A>T) is associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (ClinVar).

How common is CCND2 p.Lys270Ter (c.808A>T) in the general population?

CCND2 p.Lys270Ter (c.808A>T) is absent from gnomAD v4.1 (gnomAD).

CCND2 p.Lys270Ter

c.808A>T · rs587777619 · VCV143982

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 0.8, phastCons 1
Overall
CADD	37.0	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: CCND2
Protein: p.Lys270Ter
Coding: c.808A>T
MANE Select: NM_001759
dbSNP: rs587777619
Type: single nucleotide variant
Location: chr12:4299947 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB
Residue 270: the 'disordered' region

Full CCND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCND2 p.Lys270Asn Uncertain significance ★ ⚠ same residue
CCND2 p.Gln277Ter Pathogenic/Likely pathogenic ★★ same condition
CCND2 p.Pro281Ser Pathogenic/Likely pathogenic ★★ same condition
CCND2 p.Ser271Ter Likely pathogenic ★★ same condition
CCND2 p.Thr280Ala Pathogenic ★★ same condition
CCND2 p.Thr280Asn Pathogenic/Likely pathogenic ★★ same condition
CCND2 p.Thr280Ile Pathogenic/Likely pathogenic ★★ same condition
CCND2 p.Thr280Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition

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/ccnd2-p-lys270ter (accessed [today's date]).

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