Is CEP83 p.Ser699= (c.2097C>T) pathogenic?

CEP83 p.Ser699= (c.2097C>T) is classified Likely benign in CEP83 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). Very rare (popmax 0.0067%, eas); Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Ser699= (c.2097C>T)?

CEP83 p.Ser699= (c.2097C>T) is associated with nephronophthisis 18 (ClinVar).

How common is CEP83 p.Ser699= (c.2097C>T) in the general population?

CEP83 p.Ser699= (c.2097C>T) is very rare (popmax 0.0067%, eas) (gnomAD).

How is Nephronophthisis inherited?

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

CEP83 p.Ser699=

c.2097C>T · rs201148634 · VCV1134466

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

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 2.7	GERP 1.1, phastCons 1
Overall
CADD	11.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,786 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00292% 47/1,607,060 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,929
European (non-Finnish)	0.00332%	30,102
African / African-American	0.00267%	37,413
Remaining individualsnot grpmax-eligible	0.00161%	62,292
Finnishnot grpmax-eligible	0.00156%	63,978
South Asian	0.0011%	90,804

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.Ser699=
Coding: c.2097C>T
MANE Select: NM_016122
dbSNP: rs201148634
Type: single nucleotide variant
Location: chr12:94308822 (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-ser699 (accessed [today's date]).

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