Is CSPP1 p.Lys944= (c.2832A>G) pathogenic?

CSPP1 p.Lys944= (c.2832A>G) is classified Likely benign in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-17). Ultra-rare (popmax 0.033%, mid); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Lys944= (c.2832A>G)?

CSPP1 p.Lys944= (c.2832A>G) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Lys944= (c.2832A>G) in the general population?

CSPP1 p.Lys944= (c.2832A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

CSPP1 p.Lys944=

c.2832A>G · rs921605745 · VCV2167809

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 2.6	GERP -2, phastCons 1
Overall
CADD	8.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000754% 11/1,458,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
Admixed American	0.00502%	19,903
Remaining individualsnot grpmax-eligible	0.0016%	62,398
European (non-Finnish)	0.000424%	235,608

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.Lys944=
Coding: c.2832A>G
MANE Select: NM_001382391
dbSNP: rs921605745
Type: single nucleotide variant
Location: chr8:67172419 (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.Lys944Ter Pathogenic ★ 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
CSPP1 c.2968+1G>T Pathogenic ★★ same condition
CSPP1 c.923+1G>C 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-lys944 (accessed [today's date]).

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