Is CEP83 p.Arg511Ter (c.1531C>T) pathogenic?

CEP83 p.Arg511Ter (c.1531C>T) is classified Pathogenic/Likely pathogenic in CEP83 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00223%, eas); Associated with CEP83-related disorder.

What condition is associated with CEP83 p.Arg511Ter (c.1531C>T)?

CEP83 p.Arg511Ter (c.1531C>T) is associated with CEP83-related disorder, nephronophthisis 18 (ClinVar).

How common is CEP83 p.Arg511Ter (c.1531C>T) in the general population?

CEP83 p.Arg511Ter (c.1531C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CEP83 p.Arg511Ter

c.1531C>T · rs1162641847 · VCV1354313

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

CEP83-related disorder

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 13 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.6	GERP 1.6, phastCons 1
Overall
CADD	39.0	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 · 1/44,832 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000372% 6/1,612,966 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,832
African / African-American	0.00134%	74,798
South Asian	0.0011%	90,878
European (non-Finnish)	0.000254%	393,191

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: CEP83
Protein: p.Arg511Ter
Coding: c.1531C>T
MANE Select: NM_016122
dbSNP: rs1162641847
Type: single nucleotide variant
Location: chr12:94333528 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.90
Residue 511: a UniProt-annotated variant site (in nphp18; does not interact with cep164 and ift20)

Full CEP83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CEP83-related disorder

Also linked: nephronophthisis 18

Similar variants

CEP83 p.Arg511Pro Pathogenic/Likely pathogenic ★★ same residue
CEP83 p.Arg511Gln Uncertain significance ★★ ⚠ same residue
CEP83 p.Arg511Leu Uncertain significance ★ ⚠ same residue
CEP83 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Arg215Ter Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Gln81Ter Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Leu351Ter Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Ala232Val 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/cep83-p-arg511ter (accessed [today's date]).

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