Is CSPP1 p.Asn1063Ser (c.3188A>G) pathogenic?

CSPP1 p.Asn1063Ser (c.3188A>G) is classified Uncertain significance in CSPP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-30). Ultra-rare (popmax 0.0249%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Asn1063Ser (c.3188A>G)?

CSPP1 p.Asn1063Ser (c.3188A>G) is associated with Inborn genetic diseases, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Asn1063Ser (c.3188A>G) in the general population?

CSPP1 p.Asn1063Ser (c.3188A>G) is ultra-rare (popmax 0.0249%, nfe) (gnomAD).

CSPP1 p.Asn1063Ser

c.3188A>G · rs201884732 · VCV860310

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0249%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	18.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0249% European (non-Finnish) · 289/1,159,354 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0216%

Overall 0.0198% 315/1,589,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.034%	2,939
European (non-Finnish)grpmax	0.0249%	4,012
African / African-American	0.0054%	18,530
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,414

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn1063Ser
Coding: c.3188A>G
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs201884732
Type: single nucleotide variant
Location: chr8:67179894 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 21

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-asn1063ser (accessed [today's date]).

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