Is CCND1 p.Pro79Ser (c.235C>T) pathogenic?

CCND1 p.Pro79Ser (c.235C>T) is classified Uncertain significance in CCND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.7935); Very rare (popmax 0.00841%, amr).

How common is CCND1 p.Pro79Ser (c.235C>T) in the general population?

CCND1 p.Pro79Ser (c.235C>T) is very rare (popmax 0.00841%, amr) (gnomAD).

What do computational predictors say about CCND1 p.Pro79Ser (c.235C>T)?

AlphaMissense predicts likely pathogenic (score 0.7935) — an in-silico prediction, not a clinical call.

CCND1 p.Pro79Ser

c.235C>T · VCV4650034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00841%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7935	likely pathogenic
REVEL	0.211	benign-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP -0.68, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,965 bp · p 0.0035 · regional, not allelic
Overall
CADD	28.6	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 0.00841% Admixed American · 5/59,474 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.000687% 10/1,455,820 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00841%	11,895
Remaining individualsnot grpmax-eligible	0.0016%	62,318
South Asian	0.00111%	90,248
European (non-Finnish)	0.000255%	392,573

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: CCND1
Protein: p.Pro79Ser
Coding: c.235C>T
MANE Select: NM_053056
Type: single nucleotide variant
Location: chr11:69643067 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 11 PDB
Residue 79: the cyclin n-terminal domain; an α-helix

Full CCND1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCND1 p.Ile251Met Uncertain significance ★★ ⚠ same type
CCND1 c.415-170G>C Benign ★★ same type
CCND1 c.575-120G>A Benign ★★ same type
CCND1 c.724-205A>G Benign ★★ same type
CCND1 c.724-26A>G Benign ★★ same type
CCND1 c.*65C>A Benign ★★ same type
CCND1 p.Arg245= Benign/Likely benign ★★ same type
CCND1 p.Phe223= Benign ★★ 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/ccnd1-p-pro79ser (accessed [today's date]).

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