Is CEP83 p.Ile565Val (c.1693A>G) pathogenic?

CEP83 p.Ile565Val (c.1693A>G) is classified Uncertain significance in CEP83 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely benign (0.0598); Very rare (popmax 0.00549%, sas); Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Ile565Val (c.1693A>G)?

CEP83 p.Ile565Val (c.1693A>G) is associated with nephronophthisis 18 (ClinVar).

How common is CEP83 p.Ile565Val (c.1693A>G) in the general population?

CEP83 p.Ile565Val (c.1693A>G) is very rare (popmax 0.00549%, 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.Ile565Val (c.1693A>G)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

CEP83 p.Ile565Val

c.1693A>G · rs768675258 · VCV2043326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 18

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -4.8, phastCons 0.23
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	4.576	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00124% 20/1,613,784 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0172%	5,807
South Asiangrpmax	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0032%	31,236
Admixed American	0.00167%	59,990
European (non-Finnish)	8.47e-05%	1,179,948

Finnish 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.Ile565Val
Coding: c.1693A>G
MANE Select: NM_016122
dbSNP: rs768675258
Type: single nucleotide variant
Location: chr12:94331714 (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-ile565val (accessed [today's date]).

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