Is CSPP1 p.Asp1055= (c.3165T>C) pathogenic?

CSPP1 p.Asp1055= (c.3165T>C) is classified Benign/Likely benign in CSPP1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-01). Rare (popmax 0.462%, nfe); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Asp1055= (c.3165T>C)?

CSPP1 p.Asp1055= (c.3165T>C) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Asp1055= (c.3165T>C) in the general population?

CSPP1 p.Asp1055= (c.3165T>C) is rare (popmax 0.462%, nfe) (gnomAD).

CSPP1 p.Asp1055=

c.3165T>C · rs10112748 · VCV434844

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.462%, nfe)

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.11	GERP -5.4, phastCons 0.69
Overall
CADD	8.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.462% European (non-Finnish) · 5,381/1,163,866 alleles

Filtering AF 0.452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.448%

Overall 0.353% 5,634/1,594,980 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.462%	216
Remaining individualsnot grpmax-eligible	0.213%	469
African / African-American	0.075%	1,333
Finnishnot grpmax-eligible	0.0566%	1,766
Ashkenazi Jewishnot grpmax-eligible	0.051%	1,962
Admixed American	0.0217%	4,598
South Asian	0.00111%	90,136

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.Asp1055=
Coding: c.3165T>C
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs10112748
Type: single nucleotide variant
Location: chr8:67179871 (GRCh38)

Full CSPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp1055 (accessed [today's date]).

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