Is CEP152 p.Arg115Gln (c.344G>A) pathogenic?

CEP152 p.Arg115Gln (c.344G>A) is classified Conflicting classifications of pathogenicity in CEP152 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-07-01). AlphaMissense: likely benign (0.0629); Rare (popmax 0.468%, nfe); Associated with microcephaly 9, primary, autosomal recessive.

What condition is associated with CEP152 p.Arg115Gln (c.344G>A)?

CEP152 p.Arg115Gln (c.344G>A) is associated with microcephaly 9, primary, autosomal recessive, Seckel syndrome 5 (ClinVar).

How common is CEP152 p.Arg115Gln (c.344G>A) in the general population?

CEP152 p.Arg115Gln (c.344G>A) is rare (popmax 0.468%, nfe) (gnomAD).

What do computational predictors say about CEP152 p.Arg115Gln (c.344G>A)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

CEP152 p.Arg115Gln

c.344G>A · rs188101277 · VCV158257

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.468%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 9, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.80	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 -2.1	GERP -5.8
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	0.103	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 0.468% European (non-Finnish) · 5,521/1,179,962 alleles

Filtering AF 0.458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.453%

Overall 0.397% 6,405/1,614,096 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.468%	214
Admixed American	0.43%	233
Remaining individualsnot grpmax-eligible	0.426%	235
Finnishnot grpmax-eligible	0.253%	395
African / African-American	0.179%	560
Ashkenazi Jewishnot grpmax-eligible	0.172%	581
Middle Eastern	0.0825%	1,212
South Asian	0.00769%	13,011
East Asian	0.00223%	44,874

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.Arg115Gln
Coding: c.344G>A
MANE Select: NM_001194998
dbSNP: rs188101277
Type: single nucleotide variant
Location: chr15:48797497 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB
Residue 115: 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.Arg115Ter Pathogenic/Likely pathogenic ★★ same residue
CEP152 p.Arg115= Likely benign ★ same residue
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.Arg1309Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg267Ter Pathogenic/Likely pathogenic ★★ same condition
CEP152 p.Arg987Ter 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-arg115gln (accessed [today's date]).

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