Is CEP83 p.Arg511Pro (c.1532G>C) pathogenic?

CEP83 p.Arg511Pro (c.1532G>C) is classified Pathogenic/Likely pathogenic in CEP83 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-23). AlphaMissense: likely pathogenic (0.8515); Very rare (popmax 0.00534%, afr); Associated with CEP83-related disorder.

What condition is associated with CEP83 p.Arg511Pro (c.1532G>C)?

CEP83 p.Arg511Pro (c.1532G>C) is associated with CEP83-related disorder, nephronophthisis 18 (ClinVar).

How common is CEP83 p.Arg511Pro (c.1532G>C) in the general population?

CEP83 p.Arg511Pro (c.1532G>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CEP83 p.Arg511Pro (c.1532G>C)?

AlphaMissense predicts likely pathogenic (score 0.8515) — an in-silico prediction, not a clinical call.

CEP83 p.Arg511Pro

c.1532G>C · rs587777487 · VCV139544

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CEP83-related disorder

Computational evidence

Protein change
AlphaMissense	0.8515	likely pathogenic ✓ concordant with ClinVar · top 4% in CEP83
REVEL	0.611	indeterminate
SaProt	LLR -11.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	24.9	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 0.00534% African / African-American · 4/74,886 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,342 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,722
European (non-Finnish)	0.00153%	65,542

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.Arg511Pro
Coding: c.1532G>C
MANE Select: NM_016122
dbSNP: rs587777487
Type: single nucleotide variant
Location: chr12:94333527 (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.Arg511Ter 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-arg511pro (accessed [today's date]).

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