Is PHIP p.Cys520fs (c.1558dup) pathogenic?

PHIP p.Cys520fs (c.1558dup) is classified Likely pathogenic in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-04). No gnomAD frequency available for this variant; Associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome.

How common is PHIP p.Cys520fs (c.1558dup) in the general population?

PHIP p.Cys520fs (c.1558dup) is no gnomAD frequency available for this variant (gnomAD).

PHIP p.Cys520fs

Q: What condition is associated with PHIP p.Cys520fs (c.1558dup)?

PHIP p.Cys520fs (c.1558dup) is associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (ClinVar).

Q: How is PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome inherited?

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

c.1558dup · rs1582206547 · VCV827776

Likely pathogenic Single submitter

Classification

Likely 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

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

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 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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: PHIP
Protein: p.Cys520fs
Coding: c.1558dup
MANE Select: NM_017934
dbSNP: rs1582206547
Type: Duplication
Location: chr6:79003824 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 520: a UniProt-annotated variant site (in chujans)

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

Disease context

For PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Infancy, Neonatal

Similar variants

PHIP p.Met508fs Likely pathogenic ★ same condition
PHIP p.Thr750fs Pathogenic ★ same condition
PHIP p.Val902fs Pathogenic ★ same condition
PHIP p.Glu811_Ile812insThrProArgProSerGluGlu Uncertain significance ★ same condition
PHIP p.Gln29fs Pathogenic same condition
PHIP p.Arg110Cys Pathogenic/Likely pathogenic ★★ same condition
PHIP p.Arg178Ter Pathogenic/Likely pathogenic ★★ same condition
PHIP p.Arg255Ter Pathogenic/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/phip-p-cys520fs (accessed [today's date]).

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