Is CCNYL1 p.Leu241Phe (c.721C>T) pathogenic?

CCNYL1 p.Leu241Phe (c.721C>T) is classified Uncertain significance in CCNYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). AlphaMissense: likely pathogenic (0.9956); Absent from gnomAD v4.1.

How common is CCNYL1 p.Leu241Phe (c.721C>T) in the general population?

CCNYL1 p.Leu241Phe (c.721C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNYL1 p.Leu241Phe (c.721C>T)?

AlphaMissense predicts likely pathogenic (score 0.9956) — an in-silico prediction, not a clinical call.

CCNYL1 p.Leu241Phe

c.721C>T · rs2470306881 · VCV3140027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9956	likely pathogenic
REVEL	0.443	indeterminate
SaProt	LLR -12.96	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 8,699 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	28.2	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: CCNYL1
Protein: p.Leu241Phe
Coding: c.721C>T
MANE Select: NM_001330218
dbSNP: rs2470306881
Type: single nucleotide variant
Location: chr2:207747128 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 75.10
Residue 241: the cyclin n-terminal domain

Full CCNYL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNYL1 p.Ala24Val Uncertain significance ★ ⚠ same type
CCNYL1 p.Ala338Thr Uncertain significance ★ ⚠ same type
CCNYL1 p.Ala345Val Uncertain significance ★ ⚠ same type
CCNYL1 p.Ala44Thr Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg20Cys Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg299Cys Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg340Gly Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg353His 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/ccnyl1-p-leu241phe (accessed [today's date]).

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