Is CCND2 p.Ala252Glu (c.755C>A) pathogenic?

CCND2 p.Ala252Glu (c.755C>A) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-19). AlphaMissense: likely benign (0.1541); Absent from gnomAD v4.1.

How common is CCND2 p.Ala252Glu (c.755C>A) in the general population?

CCND2 p.Ala252Glu (c.755C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCND2 p.Ala252Glu (c.755C>A)?

AlphaMissense predicts likely benign (score 0.1541) — an in-silico prediction, not a clinical call.

CCND2 p.Ala252Glu

c.755C>A · rs781695497 · VCV1387213

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1541 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1541	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.33	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 3.4	GERP -2.4, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	17.18	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

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.Ala252Glu
Coding: c.755C>A
MANE Select: NM_001759
dbSNP: rs781695497
Type: single nucleotide variant
Location: chr12:4299894 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB

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

Similar variants

CCND2 p.Ala252= Benign/Likely benign ★★ same residue
CCND2 p.Ala252Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CCND2 p.Gln277Ter Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Pro281Ala Pathogenic ★★ same type
CCND2 p.Pro281Ser Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Ser271Ter Likely pathogenic ★★ same type
CCND2 p.Thr280Ala Pathogenic ★★ same type
CCND2 p.Thr280Asn Pathogenic/Likely pathogenic ★★ 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/ccnd2-p-ala252glu (accessed [today's date]).

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