Is CEP55 p.Arg86Ter (c.256C>T) pathogenic?

CEP55 p.Arg86Ter (c.256C>T) is classified Pathogenic in CEP55 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-09). Ultra-rare (popmax 0.0559%, nfe); Associated with Inborn genetic diseases.

How common is CEP55 p.Arg86Ter (c.256C>T) in the general population?

CEP55 p.Arg86Ter (c.256C>T) is ultra-rare (popmax 0.0559%, nfe) (gnomAD).

CEP55 p.Arg86Ter

Q: What condition is associated with CEP55 p.Arg86Ter (c.256C>T)?

CEP55 p.Arg86Ter (c.256C>T) is associated with Inborn genetic diseases, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (ClinVar).

c.256C>T · rs141458677 · VCV437875

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0559%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP -0.09, phastCons 0.8
Overall
CADD	35.0	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 0.0559% European (non-Finnish) · 659/1,179,822 alleles

Filtering AF 0.0523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0509%

Overall 0.0449% 724/1,613,690 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0559%	1,790
Admixed American	0.0384%	2,608
Remaining individualsnot grpmax-eligible	0.0304%	3,288
Finnishnot grpmax-eligible	0.0234%	4,267
African / African-American	0.00801%	12,480
East Asian	0.00223%	44,868
South Asian	0.0011%	91,074

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.Arg86Ter
Coding: c.256C>T
MANE Select: NM_018131
dbSNP: rs141458677
Type: single nucleotide variant
Location: chr10:93503185 (GRCh38)
Gene constraint: LOEUF 1.138 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 4 PDB
Residue 86: a UniProt-annotated variant site (in march)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome

Similar variants

CEP55 p.Arg86Gln Uncertain significance ★ ⚠ same residue
CEP55 p.Arg86Leu Uncertain significance ★ ⚠ same residue
CEP55 p.Arg64Ter Pathogenic/Likely pathogenic ★★ same condition
CEP55 p.Ser425Ter Pathogenic ★★ same condition
CEP55 p.Arg385Gln Uncertain significance ★★ ⚠ same condition
CEP55 p.His293Arg Uncertain significance ★★ ⚠ same condition
CEP55 p.Pro426Arg Uncertain significance ★★ ⚠ same condition
CEP55 p.Ser2Phe Uncertain significance ★★ ⚠ 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-arg86ter (accessed [today's date]).

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