Is CCND2 p.Thr190= (c.570C>G) pathogenic?

CCND2 p.Thr190= (c.570C>G) is classified Benign in CCND2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 39.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3.

What condition is associated with CCND2 p.Thr190= (c.570C>G)?

CCND2 p.Thr190= (c.570C>G) is associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (ClinVar).

CCND2 p.Thr190=

Q: How common is CCND2 p.Thr190= (c.570C>G) in the general population?

CCND2 p.Thr190= (c.570C>G) is common (popmax 39.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.570C>G · rs3217805 · VCV380772

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 39.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -4.2
Overall
CADD	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.8% European (non-Finnish) · 467,667/1,176,300 alleles

Filtering AF 39.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.6%

Overall 36.7% 590,807/1,608,466 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	42.9%	2
Ashkenazi Jewishnot grpmax-eligible	42.2%	2
European (non-Finnish)grpmax	39.8%	3
Finnishnot grpmax-eligible	36.1%	3
Middle Eastern	36%	3
Remaining individualsnot grpmax-eligible	35.1%	3
Admixed American	30.6%	3
South Asian	26.4%	4
African / African-American	19.5%	5
East Asian	14.7%	7

Amish 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
Protein: p.Thr190=
Coding: c.570C>G
MANE Select: NM_001759
dbSNP: rs3217805
Type: single nucleotide variant
Location: chr12:4278918 (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

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

Similar variants

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
CCND2 c.-49T>C Benign ★★ 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-thr190 (accessed [today's date]).

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