Is CYLD p.Phe766fs (c.2298del) pathogenic?

CYLD p.Phe766fs (c.2298del) is classified Pathogenic in CYLD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). Absent from gnomAD v4.1.

How common is CYLD p.Phe766fs (c.2298del) in the general population?

CYLD p.Phe766fs (c.2298del) is absent from gnomAD v4.1 (gnomAD).

CYLD p.Phe766fs

c.2298del · VCV4763875

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,654)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 16 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.15	GERP -4.5, phastCons 0.007

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,599,654). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CYLD
Protein: p.Phe766fs
Coding: c.2298del
MANE Select: NM_001378743
Type: Deletion
Location: chr16:50792651 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 6 PDB
Residue 766: the usp domain

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

Similar variants

CYLD p.Asp277fs Pathogenic ★★ same type
CYLD p.Lys764fs Pathogenic ★★ same type
CYLD p.Ser371fs Pathogenic/Likely pathogenic ★★ same type
CYLD p.Thr819_Cys820insTer Pathogenic ★★ same type
CYLD c.1950-5_1950-2del Uncertain significance ★★ same type
CYLD c.1950-2_1953del Pathogenic ★ same type
CYLD c.2215_2241+289del Pathogenic ★ same type
CYLD p.Asn553fs 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-phe766fs (accessed [today's date]).

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