Is CEP83 p.Arg679Cys (c.2035C>T) pathogenic?

CEP83 p.Arg679Cys (c.2035C>T) is classified Uncertain significance in CEP83 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-23). AlphaMissense: likely benign (0.2465); Ultra-rare (popmax 0.0132%, sas); Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Arg679Cys (c.2035C>T)?

CEP83 p.Arg679Cys (c.2035C>T) is associated with nephronophthisis 18 (ClinVar).

How common is CEP83 p.Arg679Cys (c.2035C>T) in the general population?

CEP83 p.Arg679Cys (c.2035C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

How is Nephronophthisis inherited?

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

What do computational predictors say about CEP83 p.Arg679Cys (c.2035C>T)?

AlphaMissense predicts likely benign (score 0.2465) — an in-silico prediction, not a clinical call.

CEP83 p.Arg679Cys

c.2035C>T · rs771273063 · VCV1444752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2465 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

nephronophthisis 18

Computational evidence

Protein change
AlphaMissense	0.2465	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.53, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	33.0	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 0.0132% South Asian · 12/91,014 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00136% 22/1,611,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,584
Admixed American	0.00167%	59,958
Remaining individualsnot grpmax-eligible	0.0016%	62,346
European (non-Finnish)	0.000679%	147,294

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.Arg679Cys
Coding: c.2035C>T
MANE Select: NM_016122
dbSNP: rs771273063
Type: single nucleotide variant
Location: chr12:94308884 (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.Arg679His Likely benign ★ ⚠ same residue
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

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-arg679cys (accessed [today's date]).

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