Is CCND2 p.Ser175Cys (c.524C>G) pathogenic?

CCND2 p.Ser175Cys (c.524C>G) is classified Benign/Likely benign in CCND2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0769); Ultra-rare (popmax 0.0508%, nfe).

How common is CCND2 p.Ser175Cys (c.524C>G) in the general population?

CCND2 p.Ser175Cys (c.524C>G) is ultra-rare (popmax 0.0508%, nfe) (gnomAD).

What do computational predictors say about CCND2 p.Ser175Cys (c.524C>G)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

CCND2 p.Ser175Cys

c.524C>G · rs143681287 · VCV507274

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0508%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -9.43	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 5.9	GERP 1.3, phastCons 0.98
Regional constraint	o/e 0.55	unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0508% European (non-Finnish) · 600/1,180,024 alleles

Filtering AF 0.0475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0461%

Overall 0.0387% 624/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0508%	1,967
Remaining individualsnot grpmax-eligible	0.024%	4,165
African / African-American	0.00934%	10,707
Admixed American	0.00167%	60,012
Finnishnot grpmax-eligible	0.00156%	63,986

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.Ser175Cys
Coding: c.524C>G
MANE Select: NM_001759
dbSNP: rs143681287
Type: single nucleotide variant
Location: chr12:4278872 (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-p-ser175cys (accessed [today's date]).

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