Is CSPP1 p.Thr679= (c.2037A>T) pathogenic?

CSPP1 p.Thr679= (c.2037A>T) is classified Likely benign in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-23). Very rare (popmax 0.00034%, nfe); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Thr679= (c.2037A>T)?

CSPP1 p.Thr679= (c.2037A>T) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Thr679= (c.2037A>T) in the general population?

CSPP1 p.Thr679= (c.2037A>T) is very rare (popmax 0.00034%, nfe) (gnomAD).

CSPP1 p.Thr679=

c.2037A>T · rs940763532 · VCV1933449

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00034%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.61, phastCons 0.4
Overall
CADD	5.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,177,630 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000249% 4/1,608,572 alleles · very rare exomes 4/1,456,276 · genomes 0/152,296 · joint denominator

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.Thr679=
Coding: c.2037A>T
MANE Select: NM_001382391
dbSNP: rs940763532
Type: single nucleotide variant
Location: chr8:67149844 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 57.34

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

Similar variants

CSPP1 p.Thr679Arg Uncertain significance ★ same residue
CSPP1 c.1022+1G>T Likely pathogenic ★★ same condition
CSPP1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.1497-2A>C Likely pathogenic ★★ same condition
CSPP1 c.1697+1G>T Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.2968+1G>A Pathogenic ★★ same condition
CSPP1 c.2968+1G>T Pathogenic ★★ same condition
CSPP1 c.923+1G>C Pathogenic ★★ same condition

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-thr679 (accessed [today's date]).

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