Is CSPP1 p.Asn908fs (c.2723del) pathogenic?

CSPP1 p.Asn908fs (c.2723del) is classified Pathogenic in CSPP1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-07-01). Ultra-rare (popmax 0.0101%, amr); Associated with CSPP1-related disorder.

What condition is associated with CSPP1 p.Asn908fs (c.2723del)?

CSPP1 p.Asn908fs (c.2723del) is associated with CSPP1-related disorder, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Asn908fs (c.2723del) in the general population?

CSPP1 p.Asn908fs (c.2723del) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

CSPP1 p.Asn908fs

c.2723del · rs863225190 · VCV217642

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Conditions

CSPP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 24 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 2.6, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% Admixed American · 6/59,262 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00552%

Overall 0.00723% 110/1,521,688 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0157%	6,356
Remaining individualsnot grpmax-eligible	0.0101%	9,856
Admixed Americangrpmax	0.0101%	9,877
European (non-Finnish)	0.00728%	13,729
South Asian	0.0068%	14,715
East Asian	0.00225%	44,438
African / African-American	0.00137%	72,992

Finnish 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.Asn908fs
Coding: c.2723del
MANE Select: NM_001382391
dbSNP: rs863225190
Type: Deletion
Location: chr8:67164396 (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

CSPP1-related disorder

Also linked: Joubert syndrome 21

Similar variants

CSPP1 p.Asn908Ser Uncertain significance ★ same residue
CSPP1 c.-54_-51del Likely pathogenic ★★ same condition
CSPP1 p.Gln753fs Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Glu11fs Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Glu755fs Pathogenic ★★ same condition
CSPP1 p.Glu89fs Pathogenic ★★ same condition
CSPP1 p.His85fs Pathogenic ★★ same condition
CSPP1 p.Ile841fs Pathogenic/Likely 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-asn908fs (accessed [today's date]).

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