Is CEP83 p.Arg276Trp (c.826C>T) pathogenic?

CEP83 p.Arg276Trp (c.826C>T) is classified Benign/Likely benign in CEP83 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1244); Common (popmax 7.56%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Arg276Trp (c.826C>T)?

CEP83 p.Arg276Trp (c.826C>T) is associated with nephronophthisis 18 (ClinVar).

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.Arg276Trp (c.826C>T)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

CEP83 p.Arg276Trp

Q: How common is CEP83 p.Arg276Trp (c.826C>T) in the general population?

CEP83 p.Arg276Trp (c.826C>T) is common (popmax 7.56%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.826C>T · rs74340001 · VCV1168156

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.56%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 18

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -9.81	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	32.0	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 7.56% European (non-Finnish) · 86,274/1,141,434 alleles

Filtering AF 7.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.5%

Overall 6.37% 98,561/1,546,866 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	7.56%	13
Remaining individualsnot grpmax-eligible	5.41%	18
Finnishnot grpmax-eligible	5.19%	19
Ashkenazi Jewishnot grpmax-eligible	4.28%	23
Middle Eastern	3.52%	28
Admixed American	2.87%	35
South Asian	2.46%	41
Amishnot grpmax-eligible	1.64%	61
African / African-American	1.25%	80
East Asian	0.021%	4,769

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.Arg276Trp
Coding: c.826C>T
MANE Select: NM_016122
dbSNP: rs74340001
Type: single nucleotide variant
Location: chr12:94375993 (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.Arg276Gln Uncertain significance ★ ⚠ same residue
CEP83 p.Arg276Pro Uncertain significance ★ ⚠ 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

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-arg276trp (accessed [today's date]).

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