Is CSPP1 p.Val1037Ile (c.3109G>A) pathogenic?

CSPP1 p.Val1037Ile (c.3109G>A) is classified Conflicting classifications of pathogenicity in CSPP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.066%, mid); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Val1037Ile (c.3109G>A)?

CSPP1 p.Val1037Ile (c.3109G>A) is associated with Inborn genetic diseases, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Val1037Ile (c.3109G>A) in the general population?

CSPP1 p.Val1037Ile (c.3109G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

CSPP1 p.Val1037Ile

c.3109G>A · rs200546493 · VCV834148

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.113	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,060 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00359% 58/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,515
Admixed American	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00288%	34,705

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.Val1037Ile
Coding: c.3109G>A
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs200546493
Type: single nucleotide variant
Location: chr8:67175436 (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-val1037ile (accessed [today's date]).

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