Is CCND2 c.571+18C>T pathogenic?

CCND2 c.571+18C>T is classified Likely benign in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). Very rare (popmax 0.00536%, afr).

How common is CCND2 c.571+18C>T in the general population?

CCND2 c.571+18C>T is very rare (popmax 0.00536%, afr) (gnomAD).

CCND2 c.571+18C>T

rs377079073 · VCV1658489

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -2.9
Overall
CADD	3.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00536% African / African-American · 4/74,624 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000752% 12/1,594,860 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0114%	8,807
African / African-Americangrpmax	0.00536%	18,656
East Asian	0.00225%	44,368

Remaining individuals 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: CCND2
Coding: c.571+18C>T
MANE Select: NM_001759
dbSNP: rs377079073
Type: single nucleotide variant
Location: chr12:4278937 (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.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
CCND2 p.Thr280Ile Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Thr280Pro 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-c-571-plus-18c-t (accessed [today's date]).

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