TMEM94 p.Pro68=
c.204G>A · rs755670959 · VCV2648252
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -12 | GERP -3.1 |
| Overall | ||
| CADD | 8.688 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,044 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00118%
19/1,613,548 alleles · ultra-rare
exomes 19/1,461,252 · genomes 0/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,044 |
| East Asian | 0.00223% | 44,868 |
| Admixed American | 0.00167% | 59,966 |
| European (non-Finnish) | 0.00136% | 73,737 |
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
- TMEM94
- Protein
- p.Pro68=
- Coding
- c.204G>A
- MANE Select
- NM_014738
- dbSNP
- rs755670959
- Type
- single nucleotide variant
- Location
- chr17:75485930 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.28 · 7 PDB
- Residue 68
- an α-helix
Similar variants
- TMEM94 p.Pro68Leu Uncertain significance ★ ⚠ same residue
- TMEM94 p.Arg264Ter Pathogenic/Likely pathogenic ★★ same type
- TMEM94 p.Arg739Ter Pathogenic ★★ same type
- TMEM94 p.Arg912Ter Pathogenic/Likely pathogenic ★★ same type
- TMEM94 p.Gln484Ter Pathogenic/Likely pathogenic ★★ same type
- TMEM94 p.Ala352Ser Uncertain significance ★★ ⚠ same type
- TMEM94 p.Ala468Thr Uncertain significance ★★ ⚠ same type
- TMEM94 p.Arg118Trp Uncertain significance ★★ ⚠ same type
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/tmem94-p-pro68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown