Is CYLD p.Asn335Ser (c.1004A>G) pathogenic?

CYLD p.Asn335Ser (c.1004A>G) is classified Benign in CYLD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.0509); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with CYLD p.Asn335Ser (c.1004A>G)?

CYLD p.Asn335Ser (c.1004A>G) is associated with ovarian cancer (ClinVar).

How common is CYLD p.Asn335Ser (c.1004A>G) in the general population?

CYLD p.Asn335Ser (c.1004A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYLD p.Asn335Ser (c.1004A>G)?

AlphaMissense predicts likely benign (score 0.0509) — an in-silico prediction, not a clinical call.

CYLD p.Asn335Ser

c.1004A>G · rs2506489175 · VCV2445285

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0509 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0509	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -4.83	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 0.32	GERP -3.6, phastCons 0.52
Regional constraint	o/e 0.86	unconstrained · MANE · 3,800 bp · p 0.045 · regional, not allelic
Overall
CADD	12.02	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

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: CYLD
Protein: p.Asn335Ser
Coding: c.1004A>G
MANE Select: NM_001378743
dbSNP: rs2506489175
Type: single nucleotide variant
Location: chr16:50776260 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 6 PDB
Residue 335: the 'interaction with trip' region; the 'disordered' region

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

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYLD p.Arg397Ser Benign ★ same condition
CYLD p.Arg235Ter Pathogenic/Likely pathogenic ★★ same type
CYLD p.Arg758Ter Pathogenic ★★ same type
CYLD p.Arg936Ter Pathogenic/Likely pathogenic ★★ same type
CYLD p.Lys767Ter Pathogenic ★★ same type
CYLD p.Ser371Ter Pathogenic ★★ same type
CYLD p.Ser839Ter Pathogenic/Likely pathogenic ★★ same type
CYLD p.Trp847Ter Pathogenic ★★ 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/cyld-p-asn335ser (accessed [today's date]).

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