Is CSPP1 p.Lys1046= (c.3138A>G) pathogenic?

CSPP1 p.Lys1046= (c.3138A>G) is classified Benign in CSPP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 5.29%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Lys1046= (c.3138A>G)?

CSPP1 p.Lys1046= (c.3138A>G) is associated with Joubert syndrome 21 (ClinVar).

CSPP1 p.Lys1046=

Q: How common is CSPP1 p.Lys1046= (c.3138A>G) in the general population?

CSPP1 p.Lys1046= (c.3138A>G) is common (popmax 5.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3138A>G · rs76567936 · VCV379767

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 5.29%, afr) — too common for a highly-penetrant pathogenic allele

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
Pangolin	Δ0.38	gain · loss 0.13 · independent
Constraint at this position
Conservation	phyloP 3.4	GERP 1.6, phastCons 0.76
Overall
CADD	17.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.29% African / African-American · 3,964/74,970 alleles

Filtering AF 5.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.09%

Overall 0.271% 4,371/1,612,298 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.29%	19
Remaining individualsnot grpmax-eligible	0.34%	294
Admixed American	0.265%	377
Middle Eastern	0.099%	1,010
South Asian	0.0077%	12,979
European (non-Finnish)	0.00195%	51,249

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.Lys1046=
Coding: c.3138A>G
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs76567936
Type: single nucleotide variant
Location: chr8:67177708 (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-lys1046 (accessed [today's date]).

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