Is CEP83 p.Arg404= (c.1212A>G) pathogenic?

CEP83 p.Arg404= (c.1212A>G) is classified Benign in CEP83 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 18.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Arg404= (c.1212A>G)?

CEP83 p.Arg404= (c.1212A>G) is associated with nephronophthisis 18 (ClinVar).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CEP83 p.Arg404=

Q: How common is CEP83 p.Arg404= (c.1212A>G) in the general population?

CEP83 p.Arg404= (c.1212A>G) is common (popmax 18.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1212A>G · rs12426243 · VCV1164928

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 18.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

nephronophthisis 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.4, phastCons 1
Overall
CADD	13.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% Admixed American · 11,065/59,988 alleles

Filtering AF 18.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 18%

Overall 10.9% 176,079/1,612,478 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	18.9%	5
Admixed Americangrpmax	18.4%	5
Ashkenazi Jewishnot grpmax-eligible	13.7%	7
Middle Eastern	12.7%	8
Finnishnot grpmax-eligible	11.5%	9
European (non-Finnish)	11.1%	9
Remaining individualsnot grpmax-eligible	10.9%	9
East Asian	9.28%	11
South Asian	7.21%	14
African / African-American	5.1%	20

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg404=
Coding: c.1212A>G
MANE Select: NM_016122
dbSNP: rs12426243
Type: single nucleotide variant
Location: chr12:94367925 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.90

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

Disease context

nephronophthisis 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

CEP83 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Arg215Ter Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Arg511Pro Pathogenic/Likely pathogenic ★★ same condition
CEP83 p.Arg511Ter 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
CEP83 p.Ala243Val 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-arg404 (accessed [today's date]).

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