TMEM138 p.Phe64=
c.192C>T · rs199841349 · VCV1533329
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00364%, nfe)
Conditions
1
Joubert syndrome 16
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.49 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.52 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00364%
European (non-Finnish) · 43/1,180,036 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00279%
45/1,614,234 alleles · very rare
exomes 44/1,461,874 · genomes 1/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00364% | 27,443 |
| Admixed American | 0.00167% | 60,026 |
| African / African-American | 0.00133% | 75,066 |
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
- TMEM138
- Protein
- p.Phe64=
- Coding
- c.192C>T
- MANE Select
- NM_016464
- dbSNP
- rs199841349
- Type
- single nucleotide variant
- Location
- chr11:61366108 (GRCh38)
- Gene constraint
- LOEUF 0.927 · pLI 0.23 (gnomAD)
- Structure
- AlphaFold pLDDT 86.42
Similar variants
- TMEM138 c.128+5G>A Pathogenic/Likely pathogenic ★★ same condition
- TMEM138 p.Ala127Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- TMEM138 p.His96Arg Pathogenic/Likely pathogenic ★★ same condition
- TMEM138 p.Tyr130Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- TMEM138 c.128+3G>T Uncertain significance ★★ same condition
- TMEM138 p.Ala126Val Uncertain significance ★★ ⚠ same condition
- TMEM138 p.Arg103Cys Uncertain significance ★★ ⚠ same condition
- TMEM138 p.Arg103His Uncertain significance ★★ ⚠ 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/tmem138-p-phe64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown