Is CCND1 p.Arg26Trp (c.76C>T) pathogenic?

CCND1 p.Arg26Trp (c.76C>T) is classified Uncertain significance in CCND1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.8212); Absent from gnomAD v4.1; Associated with familial long QT syndrome.

What condition is associated with CCND1 p.Arg26Trp (c.76C>T)?

CCND1 p.Arg26Trp (c.76C>T) is associated with familial long QT syndrome (ClinVar).

How common is CCND1 p.Arg26Trp (c.76C>T) in the general population?

CCND1 p.Arg26Trp (c.76C>T) is absent from gnomAD v4.1 (gnomAD).

How is Romano-Ward syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CCND1 p.Arg26Trp (c.76C>T)?

AlphaMissense predicts likely pathogenic (score 0.8212) — an in-silico prediction, not a clinical call.

CCND1 p.Arg26Trp

c.76C>T · VCV3358898

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8212 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.8212	likely pathogenic
REVEL	0.48	indeterminate
SaProt	LLR -12.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, 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.Arg26Trp
Coding: c.76C>T
MANE Select: NM_053056
Type: single nucleotide variant
Location: chr11:69641389 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 11 PDB
Residue 26: an α-helix

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

Disease context

familial long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Romano-Ward syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

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-arg26trp (accessed [today's date]).

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