Is CSPP1 p.Arg1100Cys (c.3298C>T) pathogenic?

CSPP1 p.Arg1100Cys (c.3298C>T) is classified Uncertain significance in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-31). Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Arg1100Cys (c.3298C>T)?

CSPP1 p.Arg1100Cys (c.3298C>T) is associated with Inborn genetic diseases, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1100Cys (c.3298C>T) in the general population?

CSPP1 p.Arg1100Cys (c.3298C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

CSPP1 p.Arg1100Cys

c.3298C>T · rs758825560 · VCV1346394

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.309	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,068 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.0013% 21/1,613,236 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00625%	16,008
South Asiangrpmax	0.00439%	22,767
European (non-Finnish)	0.0011%	90,719

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.Arg1100Cys
Coding: c.3298C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs758825560
Type: single nucleotide variant
Location: chr8:67190727 (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-arg1100cys (accessed [today's date]).

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