Is CEP83 p.Arg562Gln (c.1685G>A) pathogenic?

CEP83 p.Arg562Gln (c.1685G>A) is classified Uncertain significance in CEP83 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-13). AlphaMissense: likely benign (0.3325); Very rare (popmax 0.00267%, afr); Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Arg562Gln (c.1685G>A)?

CEP83 p.Arg562Gln (c.1685G>A) is associated with nephronophthisis 18 (ClinVar).

How common is CEP83 p.Arg562Gln (c.1685G>A) in the general population?

CEP83 p.Arg562Gln (c.1685G>A) is very rare (popmax 0.00267%, afr) (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.Arg562Gln (c.1685G>A)?

AlphaMissense predicts likely benign (score 0.3325) — an in-silico prediction, not a clinical call.

CEP83 p.Arg562Gln

c.1685G>A · rs182648141 · VCV1524610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3325 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 18

Computational evidence

Protein change
AlphaMissense	0.3325	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.91	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 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	29.2	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 0.00267% African / African-American · 2/75,018 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00149% 24/1,613,744 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,509
European (non-Finnish)	0.00178%	56,182
Admixed American	0.00167%	60,008

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.Arg562Gln
Coding: c.1685G>A
MANE Select: NM_016122
dbSNP: rs182648141
Type: single nucleotide variant
Location: chr12:94331722 (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.Arg562Ter Conflicting classifications of pathogenicity ★ 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-arg562gln (accessed [today's date]).

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