TMEM67 p.Pro381=
c.1143T>C · rs1315807334 · VCV2088925
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00278%, nfe)
Conditions
2
Joubert syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.21 | GERP 0.53, phastCons 0.002 |
| Overall | ||
| CADD | 9.082 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00278%
European (non-Finnish) · 32/1,151,122 alleles
Filtering AF
0.00201%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00172%
Overall
0.00202%
32/1,580,624 alleles · very rare
exomes 30/1,428,404 · genomes 2/152,220 · 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
- TMEM67
- Protein
- p.Pro381=
- Coding
- c.1143T>C
- MANE Select
- NM_153704
- dbSNP
- rs1315807334
- Type
- single nucleotide variant
- Location
- chr8:93785233 (GRCh38)
- Gene constraint
- LOEUF 1.079 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 1 PDB
- Residue 381
- a UniProt-annotated variant site (in jbts6); a UniProt-annotated variant site (in jbts6, mks3 and rhyns)
Similar variants
- TMEM67 c.1132-2A>G Likely pathogenic ★★ same condition
- TMEM67 c.223+1G>C Likely pathogenic ★★ same condition
- TMEM67 c.223+1G>T Pathogenic/Likely pathogenic ★★ same condition
- TMEM67 c.224-2A>T Pathogenic/Likely pathogenic ★★ same condition
- TMEM67 c.2556+1G>A Pathogenic ★★ same condition
- TMEM67 c.2764+2T>G Likely pathogenic ★★ same condition
- TMEM67 c.312+5G>A Pathogenic ★★ same condition
- TMEM67 c.869+1G>C Likely 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/tmem67-p-pro381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown