Is CEP295 p.Arg55fs (c.163_164del) pathogenic?

CEP295 p.Arg55fs (c.163164del) is classified Pathogenic in CEP295 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-22). Very rare (popmax 0.00982%, amr); Associated with Seckel syndrome 11.

What condition is associated with CEP295 p.Arg55fs (c.163_164del)?

CEP295 p.Arg55fs (c.163_164del) is associated with Seckel syndrome 11 (ClinVar).

How common is CEP295 p.Arg55fs (c.163_164del) in the general population?

CEP295 p.Arg55fs (c.163_164del) is very rare (popmax 0.00982%, amr) (gnomAD).

CEP295 p.Arg55fs

c.163_164del · rs1464608105 · VCV3062334

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00982%, amr)

Conditions

Seckel syndrome 11

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 3 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	29.7	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 0.00982% Admixed American · 5/50,904 alleles

Filtering AF 0.00383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.000645% 10/1,551,146 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00982%	10,181
European (non-Finnish)	0.000436%	229,341

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: CEP295
Protein: p.Arg55fs
Coding: c.163_164del
MANE Select: NM_033395
dbSNP: rs1464608105
Type: Microsatellite
Location: chr11:93667659 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.76
Residue 55: the 'necessary for centriole targeting and microtubule association' region

Full CEP295 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Seckel syndrome 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP295 p.Gln998Arg Uncertain significance ★★ ⚠ same condition
CEP295 p.Ala2429fs Likely pathogenic ★ same condition
CEP295 p.Glu1544fs Likely pathogenic ★ same condition
CEP295 p.Glu764Ter Likely pathogenic ★ same condition
CEP295 p.Pro1762Arg Likely benign ★ same condition
CEP295 p.Arg1520Ter Pathogenic same condition
CEP295 p.Gln544Ter Pathogenic same condition
CEP295 p.Pro562Leu 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/cep295-p-arg55fs (accessed [today's date]).

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