Is CSPP1 p.Ala1118= (c.3354A>G) pathogenic?

CSPP1 p.Ala1118= (c.3354A>G) is classified Likely benign in CSPP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-01). Very rare (popmax 0.00669%, eas); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Ala1118= (c.3354A>G)?

CSPP1 p.Ala1118= (c.3354A>G) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Ala1118= (c.3354A>G) in the general population?

CSPP1 p.Ala1118= (c.3354A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

CSPP1 p.Ala1118=

c.3354A>G · rs557509288 · VCV2062083

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

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 -0.12	GERP 1.6
Overall
CADD	4.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,868 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000682% 11/1,613,504 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,956
African / African-American	0.00666%	15,007
Remaining individualsnot grpmax-eligible	0.0048%	20,823

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.Ala1118=
Coding: c.3354A>G
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs557509288
Type: single nucleotide variant
Location: chr8:67193487 (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-ala1118 (accessed [today's date]).

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