Is CEP290 p.Ser31= (c.93C>T) pathogenic?

CEP290 p.Ser31= (c.93C>T) is classified Likely benign in CEP290 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-28). Ultra-rare (popmax 0.0335%, afr); Associated with Joubert syndrome.

What condition is associated with CEP290 p.Ser31= (c.93C>T)?

CEP290 p.Ser31= (c.93C>T) is associated with Joubert syndrome, Joubert syndrome 5, Senior-Loken syndrome 6 (ClinVar).

How common is CEP290 p.Ser31= (c.93C>T) in the general population?

CEP290 p.Ser31= (c.93C>T) is ultra-rare (popmax 0.0335%, afr) (gnomAD).

CEP290 p.Ser31=

c.93C>T · rs375955381 · VCV1136945

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, afr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -4.9
Overall
CADD	7.932	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% African / African-American · 25/74,640 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00168% 27/1,607,410 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0335%	2,986
Admixed American	0.00169%	59,012
Remaining individualsnot grpmax-eligible	0.00161%	62,210

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: CEP290
Protein: p.Ser31=
Coding: c.93C>T
MANE Select: NM_025114
dbSNP: rs375955381
Type: single nucleotide variant
Location: chr12:88141215 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 31: the 'self-association (with itself or c-terminus)' region

Full CEP290 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 5 Senior-Loken syndrome 6 Meckel syndrome, type 4 Leber congenital amaurosis 10 Bardet-Biedl syndrome 14 Meckel syndrome nephronophthisis

Similar variants

CEP290 p.Ser31Pro Uncertain significance ★ ⚠ same residue
CEP290 p.Ser31Phe Uncertain significance ⚠ same residue
CEP290 c.1189+1G>A Pathogenic ★★★ same condition
CEP290 c.1189+2T>C Pathogenic ★★★ same condition
CEP290 c.297+1G>T Pathogenic ★★★ same condition
CEP290 c.2991+1655A>G Pathogenic ★★★ same condition
CEP290 c.6271-8T>G Pathogenic ★★★ same condition
CEP290 p.Arg1272Ter 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/cep290-p-ser31 (accessed [today's date]).

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