TMEM216 p.Phe76=
c.228T>C · rs1383356739 · VCV1367455
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00769%, sas)
Conditions
1
Joubert syndrome
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 -0.4 | GERP -3.1, phastCons 0.21 |
| Overall | ||
| CADD | 9.641 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,080 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.000479%
7/1,461,476 alleles · very rare
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
- TMEM216
- Protein
- p.Phe76=
- Coding
- c.228T>C
- MANE Select
- NM_001173990
- dbSNP
- rs1383356739
- Type
- single nucleotide variant
- Location
- chr11:61393975 (GRCh38)
- Gene constraint
- LOEUF 1.453 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.18
Similar variants
- TMEM216 p.Phe76Ile Uncertain significance ★ same residue
- TMEM216 c.137-1G>A Likely pathogenic ★★ same condition
- TMEM216 c.137-2A>G Likely pathogenic ★★ same condition
- TMEM216 c.229+1G>A Likely pathogenic ★★ same condition
- TMEM216 c.230-2A>G Likely pathogenic ★★ same condition
- TMEM216 c.34+2T>C Likely pathogenic ★★ same condition
- TMEM216 p.Arg73His Pathogenic/Likely pathogenic ★★ same condition
- TMEM216 p.Arg73Leu 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/tmem216-p-phe76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown