Is CCNYL1 p.Pro72Arg (c.215C>G) pathogenic?

CCNYL1 p.Pro72Arg (c.215C>G) is classified Uncertain significance in CCNYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely pathogenic (0.5956); Very rare (popmax 0.00213%, nfe).

How common is CCNYL1 p.Pro72Arg (c.215C>G) in the general population?

CCNYL1 p.Pro72Arg (c.215C>G) is very rare (popmax 0.00213%, nfe) (gnomAD).

What do computational predictors say about CCNYL1 p.Pro72Arg (c.215C>G)?

AlphaMissense predicts likely pathogenic (score 0.5956) — an in-silico prediction, not a clinical call.

CCNYL1 p.Pro72Arg

c.215C>G · VCV4650153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00213%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5956	likely pathogenic
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 30 kb · p 0.014 · regional, not allelic
Overall
CADD	21.8	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 0.00213% European (non-Finnish) · 25/1,173,580 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00124%

Overall 0.00156% 25/1,598,428 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.Pro72Arg
Coding: c.215C>G
MANE Select: NM_001330218
Type: single nucleotide variant
Location: chr2:207712111 (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.Pro72Thr Uncertain significance ★ ⚠ same residue
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

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-pro72arg (accessed [today's date]).

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