Is CEP83 p.Glu69Lys (c.205G>A) pathogenic?

CEP83 p.Glu69Lys (c.205G>A) is classified Uncertain significance in CEP83 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-14). AlphaMissense: likely benign (0.1237); Ultra-rare (popmax 0.0179%, eas); Associated with Inborn genetic diseases.

What condition is associated with CEP83 p.Glu69Lys (c.205G>A)?

CEP83 p.Glu69Lys (c.205G>A) is associated with Inborn genetic diseases, nephronophthisis 18 (ClinVar).

How common is CEP83 p.Glu69Lys (c.205G>A) in the general population?

CEP83 p.Glu69Lys (c.205G>A) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

What do computational predictors say about CEP83 p.Glu69Lys (c.205G>A)?

AlphaMissense predicts likely benign (score 0.1237) — an in-silico prediction, not a clinical call.

CEP83 p.Glu69Lys

c.205G>A · rs748739528 · VCV2159017

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1237 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1237	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -7.80	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 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	25.4	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 0.0179% East Asian · 8/44,722 alleles

Filtering AF 0.00886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00643%

Overall 0.000685% 10/1,460,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,590
Remaining individualsnot grpmax-eligible	0.0032%	31,218

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.Glu69Lys
Coding: c.205G>A
MANE Select: NM_016122
dbSNP: rs748739528
Type: single nucleotide variant
Location: chr12:94411816 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 18

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-glu69lys (accessed [today's date]).

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