Is CSPP1 p.Pro1053Ser (c.3157C>T) pathogenic?

CSPP1 p.Pro1053Ser (c.3157C>T) is classified Uncertain significance in CSPP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-05). Ultra-rare (popmax 0.0167%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Pro1053Ser (c.3157C>T)?

CSPP1 p.Pro1053Ser (c.3157C>T) is associated with Inborn genetic diseases, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Pro1053Ser (c.3157C>T) in the general population?

CSPP1 p.Pro1053Ser (c.3157C>T) is ultra-rare (popmax 0.0167%, nfe) (gnomAD).

CSPP1 p.Pro1053Ser

c.3157C>T · rs371681100 · VCV861929

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.03	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP -2.7, phastCons 0.97
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	14.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% European (non-Finnish) · 194/1,159,882 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.0128% 203/1,589,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0167%	5,979
Remaining individualsnot grpmax-eligible	0.00972%	10,290
Admixed American	0.00168%	59,480
Finnishnot grpmax-eligible	0.00158%	63,466
African / African-American	0.00135%	74,340

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.Pro1053Ser
Coding: c.3157C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs371681100
Type: single nucleotide variant
Location: chr8:67179863 (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-pro1053ser (accessed [today's date]).

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