Is CYLD p.His298= (c.894C>T) pathogenic?

CYLD p.His298= (c.894C>T) is classified Likely benign in CYLD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-30). Ultra-rare (popmax 0.0112%, eas).

How common is CYLD p.His298= (c.894C>T) in the general population?

CYLD p.His298= (c.894C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

CYLD p.His298=

c.894C>T · VCV4804973

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -3.4, phastCons 0.41
Overall
CADD	6.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,792 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00112% 18/1,608,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0145%	6,918
East Asiangrpmax	0.0112%	8,958
African / African-American	0.00134%	74,794
European (non-Finnish)	0.000255%	391,696

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CYLD
Protein: p.His298=
Coding: c.894C>T
MANE Select: NM_001378743
Type: single nucleotide variant
Location: chr16:50754405 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.06 · 6 PDB
Residue 298: the 'interaction with trip' region; a β-strand

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

Similar variants

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
CYLD c.*3229C>T 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/cyld-p-his298 (accessed [today's date]).

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