Is CCND2 p.Arg178Cys (c.532C>T) pathogenic?

CCND2 p.Arg178Cys (c.532C>T) is classified Uncertain significance in CCND2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely benign (0.2261); Very rare (popmax 0.00153%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CCND2 p.Arg178Cys (c.532C>T)?

CCND2 p.Arg178Cys (c.532C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCND2 p.Arg178Cys (c.532C>T) in the general population?

CCND2 p.Arg178Cys (c.532C>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about CCND2 p.Arg178Cys (c.532C>T)?

AlphaMissense predicts likely benign (score 0.2261) — an in-silico prediction, not a clinical call.

CCND2 p.Arg178Cys

c.532C>T · rs1488421614 · VCV2619766

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2261	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	26.6	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 0.00153% European (non-Finnish) · 18/1,179,988 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00123% 18/1,461,692 alleles · very rare

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: CCND2
Protein: p.Arg178Cys
Coding: c.532C>T
MANE Select: NM_001759
dbSNP: rs1488421614
Type: single nucleotide variant
Location: chr12:4278880 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCND2 p.Pro281Ala Pathogenic ★★ same condition
CCND2 p.Ser222Leu Uncertain significance ★★ ⚠ same condition
CCND2 p.Gln215Ter Pathogenic ★ same condition
CCND2 p.Glu272Ter Pathogenic ★ same condition
CCND2 p.Ala120Ser Uncertain significance ★ ⚠ same condition
CCND2 p.Ala189Val Uncertain significance ★ ⚠ same condition
CCND2 p.Ala195Gly Uncertain significance ★ same condition
CCND2 p.Arg266His Uncertain significance ★ ⚠ 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-arg178cys (accessed [today's date]).

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