Is CSPP1 p.Ser1129= (c.3387T>C) pathogenic?

CSPP1 p.Ser1129= (c.3387T>C) is classified Likely benign in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-25). Very rare (popmax 0.000339%, nfe); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Ser1129= (c.3387T>C)?

CSPP1 p.Ser1129= (c.3387T>C) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Ser1129= (c.3387T>C) in the general population?

CSPP1 p.Ser1129= (c.3387T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

CSPP1 p.Ser1129=

c.3387T>C · rs2129575946 · VCV1121450

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Joubert syndrome 21

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.44	GERP -1, phastCons 0.19
Overall
CADD	6.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,178,842 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,900 alleles · very rare exomes 4/1,460,546 · genomes 0/152,354 · joint denominator

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.Ser1129=
Coding: c.3387T>C
MANE Select: NM_001382391
dbSNP: rs2129575946
Type: single nucleotide variant
Location: chr8:67193520 (GRCh38)

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

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-ser1129 (accessed [today's date]).

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