Is CYLD p.Ser371fs (c.1111del) pathogenic?

CYLD p.Ser371fs (c.1111del) is classified Pathogenic/Likely pathogenic in CYLD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-12). Absent from gnomAD; Associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 8.

What condition is associated with CYLD p.Ser371fs (c.1111del)?

CYLD p.Ser371fs (c.1111del) is associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 8 (ClinVar).

How common is CYLD p.Ser371fs (c.1111del) in the general population?

CYLD p.Ser371fs (c.1111del) is absent from gnomAD (gnomAD).

CYLD p.Ser371fs

Q: How is Frontotemporal dementia with motor neuron disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1111del · rs2506514993 · VCV2681079

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

frontotemporal dementia and/or amyotrophic lateral sclerosis 8

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 8 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -2.4, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser371fs
Coding: c.1111del
MANE Select: NM_001378743
dbSNP: rs2506514993
Type: Deletion
Location: chr16:50777914 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 6 PDB
Residue 371: the 'interaction with trip' region

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

Disease context

frontotemporal dementia and/or amyotrophic lateral sclerosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Frontotemporal dementia with motor neuron disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CYLD p.Ser371Ter Pathogenic ★★ same residue
CYLD p.Arg936Ter Pathogenic/Likely pathogenic ★★ same condition
CYLD p.Lys767Ter Pathogenic ★★ same condition
CYLD p.Ala217Thr Uncertain significance ★★ ⚠ same condition
CYLD p.Arg147Cys Uncertain significance ★★ ⚠ same condition
CYLD p.Arg53His Uncertain significance ★★ ⚠ same condition
CYLD p.Ile232Val Uncertain significance ★★ ⚠ same condition
CYLD p.Ile588Thr Uncertain significance ★★ ⚠ same condition

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-ser371fs (accessed [today's date]).

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