Is USP7 p.Cys488fs (c.1463del) pathogenic?

USP7 p.Cys488fs (c.1463del) is classified Pathogenic in USP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). No gnomAD frequency available for this variant; Associated with Hao-Fountain syndrome due to USP7 mutation.

What condition is associated with USP7 p.Cys488fs (c.1463del)?

USP7 p.Cys488fs (c.1463del) is associated with Hao-Fountain syndrome due to USP7 mutation (ClinVar).

How common is USP7 p.Cys488fs (c.1463del) in the general population?

USP7 p.Cys488fs (c.1463del) is no gnomAD frequency available for this variant (gnomAD).

USP7 p.Cys488fs

c.1463del · rs2549229217 · VCV3255088

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Hao-Fountain syndrome due to USP7 mutation

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 14 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -4.8, phastCons 0.012

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: USP7
Protein: p.Cys488fs
Coding: c.1463del
MANE Select: NM_003470
dbSNP: rs2549229217
Type: Deletion
Location: chr16:8905297 (GRCh38)
Gene constraint: LOEUF 0.085 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 86 PDB
Residue 488: the usp domain; a UniProt-annotated variant site (in hafous; when expressed in usp7-deficient cells does not rescue defective endosomal protein recycling and reduced f-actin levels)

Full USP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hao-Fountain syndrome due to USP7 mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hao-Fountain syndrome (Orphanet):

Onset: Infancy, Neonatal

Similar variants

USP7 p.Lys801fs Likely pathogenic ★ same condition
USP7 p.Arg1018Ter Pathogenic/Likely pathogenic ★★ same condition
USP7 p.Arg508Ter Pathogenic ★★ same condition
USP7 p.Arg793Cys Uncertain significance ★★ ⚠ same condition
USP7 c.2919+1G>A Likely pathogenic ★ same condition
USP7 c.3040-1G>A Likely pathogenic ★ same condition
USP7 c.3111+1G>A Pathogenic ★ same condition
USP7 p.Arg1023Ter Likely pathogenic ★ 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/usp7-p-cys488fs (accessed [today's date]).

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