Is CEP152 p.Arg1586Pro (c.4757G>C) pathogenic?

CEP152 p.Arg1586Pro (c.4757G>C) is classified Conflicting classifications of pathogenicity in CEP152 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0971); Rare (popmax 0.441%, eas); Associated with Seckel syndrome 5.

What condition is associated with CEP152 p.Arg1586Pro (c.4757G>C)?

CEP152 p.Arg1586Pro (c.4757G>C) is associated with Seckel syndrome 5, microcephaly 9, primary, autosomal recessive (ClinVar).

How common is CEP152 p.Arg1586Pro (c.4757G>C) in the general population?

CEP152 p.Arg1586Pro (c.4757G>C) is rare (popmax 0.441%, eas) (gnomAD).

What do computational predictors say about CEP152 p.Arg1586Pro (c.4757G>C)?

AlphaMissense predicts likely benign (score 0.0971) — an in-silico prediction, not a clinical call.

CEP152 p.Arg1586Pro

c.4757G>C · rs202237336 · VCV384842

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0971 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.441%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Seckel syndrome 5

Computational evidence

Protein change
AlphaMissense	0.0971	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -8.6
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.441% East Asian · 198/44,872 alleles

Filtering AF 0.391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.372%

Overall 0.0167% 270/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.441%	227
Remaining individualsnot grpmax-eligible	0.0512%	1,953
South Asian	0.0253%	3,960
African / African-American	0.02%	5,003
Middle Eastern	0.0165%	6,062
Admixed American	0.00167%	60,020

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.Arg1586Pro
Coding: c.4757G>C
MANE Select: NM_001194998
dbSNP: rs202237336
Type: single nucleotide variant
Location: chr15:48738625 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB

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

Disease context

Seckel syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly 9, primary, autosomal recessive

Similar variants

CEP152 c.1908+1G>T Likely pathogenic ★★ same condition
CEP152 c.540+1G>A Pathogenic/Likely pathogenic ★★ same condition
CEP152 c.972+2T>A Likely pathogenic ★★ same condition
CEP152 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg1309Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg267Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg987Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Gln265Pro 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-arg1586pro (accessed [today's date]).

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