Is CCNE1 p.Pro295Ser (c.883C>T) pathogenic?

CCNE1 p.Pro295Ser (c.883C>T) is classified Likely benign in CCNE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.0687); Ultra-rare (popmax 0.0335%, nfe).

How common is CCNE1 p.Pro295Ser (c.883C>T) in the general population?

CCNE1 p.Pro295Ser (c.883C>T) is ultra-rare (popmax 0.0335%, nfe) (gnomAD).

What do computational predictors say about CCNE1 p.Pro295Ser (c.883C>T)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

CCNE1 p.Pro295Ser

c.883C>T · VCV3487409

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.46	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 -0.52	GERP -4.2
Regional constraint	o/e 0.76	unconstrained · MANE · 6,565 bp · p 9.6e-07 · regional, not allelic
Overall
CADD	0.133	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 0.0335% European (non-Finnish) · 395/1,180,038 alleles

Filtering AF 0.0307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0253% 409/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0335%	2,987
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00534%	18,730
Admixed American	0.00167%	59,990
Finnishnot grpmax-eligible	0.00156%	63,992

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: CCNE1
Protein: p.Pro295Ser
Coding: c.883C>T
MANE Select: NM_001238
Type: single nucleotide variant
Location: chr19:29822282 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.13 · 22 PDB

Full CCNE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNE1 p.Ala111Gly Uncertain significance ★ ⚠ same type
CCNE1 p.Ala178Val Uncertain significance ★ ⚠ same type
CCNE1 p.Ala22Val Uncertain significance ★ ⚠ same type
CCNE1 p.Arg13Trp Uncertain significance ★ ⚠ same type
CCNE1 p.Arg350Gly Uncertain significance ★ ⚠ same type
CCNE1 p.Arg5Cys Uncertain significance ★ ⚠ same type
CCNE1 p.Arg5Leu Uncertain significance ★ ⚠ same type
CCNE1 p.Arg85Gln Uncertain significance ★ ⚠ 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/ccne1-p-pro295ser (accessed [today's date]).

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