Is CEP135 p.Arg955Ter (c.2863C>T) pathogenic?

CEP135 p.Arg955Ter (c.2863C>T) is classified Pathogenic in CEP135 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00223%, eas); Associated with microcephaly 8, primary, autosomal recessive.

What condition is associated with CEP135 p.Arg955Ter (c.2863C>T)?

CEP135 p.Arg955Ter (c.2863C>T) is associated with microcephaly 8, primary, autosomal recessive (ClinVar).

How common is CEP135 p.Arg955Ter (c.2863C>T) in the general population?

CEP135 p.Arg955Ter (c.2863C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CEP135 p.Arg955Ter

c.2863C>T · rs1730824213 · VCV1012268

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

microcephaly 8, primary, autosomal recessive

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 22 of 26
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -3.8, phastCons 1
Overall
CADD	36.0	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 0.00223% East Asian · 1/44,834 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000342% 5/1,461,432 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,834
South Asian	0.0022%	45,504
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	8.48e-05%	1,179,906

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: CEP135
Protein: p.Arg955Ter
Coding: c.2863C>T
MANE Select: NM_025009
dbSNP: rs1730824213
Type: single nucleotide variant
Location: chr4:56017708 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.15 · 2 PDB

Full CEP135 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 8, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP135 p.Arg955Gln Uncertain significance ★ ⚠ same residue
CEP135 p.Arg955= Likely benign ★ same residue
CEP135 c.473-1G>C Likely pathogenic ★★ same condition
CEP135 p.Arg1083Ter Pathogenic/Likely pathogenic ★★ same condition
CEP135 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same condition
CEP135 p.Arg418Ter Pathogenic ★★ same condition
CEP135 p.Arg470Ter Pathogenic/Likely pathogenic ★★ same condition
CEP135 p.Arg908Ter 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/cep135-p-arg955ter (accessed [today's date]).

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