Is CCNYL1 p.Arg340Gly (c.1018A>G) pathogenic?

CCNYL1 p.Arg340Gly (c.1018A>G) is classified Uncertain significance in CCNYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: ambiguous (0.4083); Very rare (popmax 0.00334%, amr).

How common is CCNYL1 p.Arg340Gly (c.1018A>G) in the general population?

CCNYL1 p.Arg340Gly (c.1018A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CCNYL1 p.Arg340Gly (c.1018A>G)?

AlphaMissense predicts ambiguous (score 0.4083) — an in-silico prediction, not a clinical call.

CCNYL1 p.Arg340Gly

c.1018A>G · VCV3997722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4083	ambiguous
REVEL	0.171	moderately benign-leaning
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -3.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,725 bp · p 0.41 · regional, not allelic
Overall
CADD	22.0	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 0.00334% Admixed American · 2/59,938 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,012 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,969
Remaining individualsnot grpmax-eligible	0.0032%	31,224
European (non-Finnish)	8.48e-05%	1,179,526

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.Arg340Gly
Coding: c.1018A>G
MANE Select: NM_001330218
Type: single nucleotide variant
Location: chr2:207753636 (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.Arg20Cys Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg299Cys 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-arg340gly (accessed [today's date]).

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