Is TCTN1 p.Pro577= (c.1731A>G) pathogenic?

TCTN1 p.Pro577= (c.1731A>G) is classified Likely benign in TCTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). Very rare (popmax 0.000678%, nfe); Associated with Joubert syndrome.

What condition is associated with TCTN1 p.Pro577= (c.1731A>G)?

TCTN1 p.Pro577= (c.1731A>G) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is TCTN1 p.Pro577= (c.1731A>G) in the general population?

TCTN1 p.Pro577= (c.1731A>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

TCTN1 p.Pro577=

c.1731A>G · rs748758027 · VCV2091314

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.343	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.019	GERP -2.1, phastCons 0.001
Overall
CADD	6.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,054 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,240 alleles · very rare exomes 8/1,461,856 · genomes 0/152,384 · 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: TCTN1
Protein: p.Pro577=
Coding: c.1731A>G
MANE Select: NM_001082538
dbSNP: rs748758027
Type: single nucleotide variant
Location: chr12:110647844 (GRCh38)
Gene constraint: LOEUF 1.133 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.10

Full TCTN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: Meckel syndrome

Similar variants

TCTN1 c.1494+1G>A Likely pathogenic ★★ same condition
TCTN1 c.1494+2T>C Likely pathogenic ★★ same condition
TCTN1 c.341+1G>A Likely pathogenic ★★ same condition
TCTN1 c.342-2A>C Pathogenic ★★ same condition
TCTN1 c.712+1G>A Likely pathogenic ★★ same condition
TCTN1 c.713-2A>G Likely pathogenic ★★ same condition
TCTN1 c.822+1G>A Pathogenic/Likely pathogenic ★★ same condition
TCTN1 p.Arg300Ter 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/tctn1-p-pro577 (accessed [today's date]).

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