Is CEP55 p.Ile172fs (c.514dup) pathogenic?

CEP55 p.Ile172fs (c.514dup) is classified Pathogenic in CEP55 (ClinVar, Single submitter, 3 submitters; last evaluated 2022-01-25). Very rare (popmax 0.000175%, nfe); Associated with multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome.

How common is CEP55 p.Ile172fs (c.514dup) in the general population?

CEP55 p.Ile172fs (c.514dup) is very rare (popmax 0.000175%, nfe) (gnomAD).

CEP55 p.Ile172fs

Q: What condition is associated with CEP55 p.Ile172fs (c.514dup)?

CEP55 p.Ile172fs (c.514dup) is associated with multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (ClinVar).

c.514dup · rs1169095680 · VCV562113

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Conditions

multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000175% European (non-Finnish) · 2/1,141,284 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00131% 2/152,172 alleles · very rare

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: CEP55
Protein: p.Ile172fs
Coding: c.514dup
MANE Select: NM_018131
dbSNP: rs1169095680
Type: Duplication
Location: chr10:93507039 (GRCh38)
Gene constraint: LOEUF 1.138 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 4 PDB
Residue 172: a UniProt-annotated variant site (in march); the 'interaction with tsg101' region; the 'interaction with pdcd6ip' region; an α-helix

Full CEP55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP55 p.Ile172Val Benign ★★ same residue
CEP55 p.Ile172Thr Uncertain significance ★ ⚠ same residue
CEP55 p.Arg64Ter Pathogenic/Likely pathogenic ★★ same condition
CEP55 p.Arg86Ter Pathogenic ★★ same condition
CEP55 p.Ser425Ter Pathogenic ★★ same condition
CEP55 p.Pro426Arg Uncertain significance ★★ ⚠ same condition
CEP55 p.Val127Ile Uncertain significance ★★ ⚠ same condition
CEP55 c.1191+89A>G Benign ★★ 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/cep55-p-ile172fs (accessed [today's date]).

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