Is CCNYL1 p.Arg20Cys (c.58C>T) pathogenic?

CCNYL1 p.Arg20Cys (c.58C>T) is classified Uncertain significance in CCNYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.1508); Very rare (popmax 0.000744%, nfe).

How common is CCNYL1 p.Arg20Cys (c.58C>T) in the general population?

CCNYL1 p.Arg20Cys (c.58C>T) is very rare (popmax 0.000744%, nfe) (gnomAD).

What do computational predictors say about CCNYL1 p.Arg20Cys (c.58C>T)?

AlphaMissense predicts likely benign (score 0.1508) — an in-silico prediction, not a clinical call.

CCNYL1 p.Arg20Cys

c.58C>T · rs1371338446 · VCV2337548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000744%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1508	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -9.94	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 1.2	GERP 0.32, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 30 kb · p 0.014 · regional, not allelic
Overall
CADD	19.97	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.000744% European (non-Finnish) · 8/1,074,826 alleles

Filtering AF 0.00032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000231%

Overall 0.000641% 8/1,248,994 alleles · very rare

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: CCNYL1
Protein: p.Arg20Cys
Coding: c.58C>T
MANE Select: NM_001330218
dbSNP: rs1371338446
Type: single nucleotide variant
Location: chr2:207711954 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 75.10

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.Arg299Cys Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg340Gly Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg353His Uncertain significance ★ ⚠ same type
CCNYL1 p.Asp54Tyr 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-arg20cys (accessed [today's date]).

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