Is CSPP1 p.Ser1092Leu (c.3275C>T) pathogenic?

CSPP1 p.Ser1092Leu (c.3275C>T) is classified Conflicting classifications of pathogenicity in CSPP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-28). Rare (popmax 0.329%, mid); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Ser1092Leu (c.3275C>T)?

CSPP1 p.Ser1092Leu (c.3275C>T) is associated with Inborn genetic diseases, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Ser1092Leu (c.3275C>T) in the general population?

CSPP1 p.Ser1092Leu (c.3275C>T) is rare (popmax 0.329%, mid) (gnomAD).

CSPP1 p.Ser1092Leu

c.3275C>T · rs768603321 · VCV840138

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.329%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 0.66
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.329% Middle Eastern · 20/6,082 alleles

Filtering AF 0.218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.00353% 57/1,614,026 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.329%	304
Remaining individualsnot grpmax-eligible	0.0096%	10,415
African / African-American	0.00667%	14,983
South Asian	0.0022%	45,539
European (non-Finnish)	0.00195%	51,305
Admixed American	0.00167%	60,000

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.Ser1092Leu
Coding: c.3275C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs768603321
Type: single nucleotide variant
Location: chr8:67190704 (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-ser1092leu (accessed [today's date]).

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