Is CEP152 p.Ser590fs (c.1768del) pathogenic?

CEP152 p.Ser590fs (c.1768del) is classified Likely pathogenic in CEP152 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Very rare (popmax 8.48e-05%, nfe); Associated with microcephaly 9, primary, autosomal recessive.

What condition is associated with CEP152 p.Ser590fs (c.1768del)?

CEP152 p.Ser590fs (c.1768del) is associated with microcephaly 9, primary, autosomal recessive, Seckel syndrome 5 (ClinVar).

How common is CEP152 p.Ser590fs (c.1768del) in the general population?

CEP152 p.Ser590fs (c.1768del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CEP152 p.Ser590fs

c.1768del · VCV3577347

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

microcephaly 9, primary, autosomal recessive

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 13 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.7	GERP 3.1, phastCons 0.002

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,864 alleles

Overall 6.85e-05% 1/1,460,408 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: CEP152
Protein: p.Ser590fs
Coding: c.1768del
MANE Select: NM_001194998
Type: Deletion
Location: chr15:48772501 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB
Residue 590: the 'disordered' region

Full CEP152 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 9, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Seckel syndrome 5

Similar variants

CEP152 p.Ser590Asn Uncertain significance ★ ⚠ same residue
CEP152 p.Ser590Gly Uncertain significance ★ ⚠ same residue
CEP152 p.Gln1058fs Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Leu1071fs Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Thr1006fs Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Thr386fs Pathogenic ★★ same condition
CEP152 p.Tyr678_Gln679delinsTer Pathogenic ★★ same condition
CEP152 p.Val1084fs 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/cep152-p-ser590fs (accessed [today's date]).

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