Is CCND1 p.Ser111Phe (c.332C>T) pathogenic?

CCND1 p.Ser111Phe (c.332C>T) is classified Uncertain significance in CCND1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1.

How common is CCND1 p.Ser111Phe (c.332C>T) in the general population?

CCND1 p.Ser111Phe (c.332C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCND1 p.Ser111Phe (c.332C>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

CCND1 p.Ser111Phe

c.332C>T · VCV3829082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 1% in CCND1
REVEL	0.482	indeterminate
SaProt	LLR -15.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,965 bp · p 0.0035 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCND1
Protein: p.Ser111Phe
Coding: c.332C>T
MANE Select: NM_053056
Type: single nucleotide variant
Location: chr11:69643164 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 11 PDB
Residue 111: 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-ser111phe (accessed [today's date]).

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