Is CSPP1 p.Arg92= (c.274C>A) pathogenic?

CSPP1 p.Arg92= (c.274C>A) is classified Likely benign in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-29). Very rare (popmax 0.00551%, afr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg92= (c.274C>A)?

CSPP1 p.Arg92= (c.274C>A) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg92= (c.274C>A) in the general population?

CSPP1 p.Arg92= (c.274C>A) is very rare (popmax 0.00551%, afr) (gnomAD).

CSPP1 p.Arg92=

c.274C>A · rs367889164 · VCV2718836

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00551%, afr)

Conditions

Joubert syndrome 21

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 2.1	GERP 1.7, phastCons 1
Overall
CADD	10.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00551% African / African-American · 4/72,540 alleles

Filtering AF 0.00179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.000938% 14/1,491,968 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00551%	18,135
European (non-Finnish)	0.000935%	106,910

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: CSPP1
Protein: p.Arg92=
Coding: c.274C>A
MANE Select: NM_001382391
dbSNP: rs367889164
Type: single nucleotide variant
Location: chr8:67086081 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 57.34

Full CSPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSPP1 p.Arg92Trp Uncertain significance ★★ same residue
CSPP1 p.Arg92Gln Uncertain significance ★ same residue
CSPP1 p.Arg92Pro Uncertain significance ★ same residue
CSPP1 c.1022+1G>T Likely pathogenic ★★ same condition
CSPP1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.1497-2A>C Likely pathogenic ★★ same condition
CSPP1 c.1697+1G>T Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.2968+1G>A 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/cspp1-p-arg92 (accessed [today's date]).

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