TMEM94 p.Pro623=
c.1869C>T · VCV4936996
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 -20 | GERP -3.4 |
| Overall | ||
| CADD | 1.383 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,996 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00149%
24/1,609,220 alleles · ultra-rare
exomes 22/1,457,030 · genomes 2/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,615 |
| East Asian | 0.00223% | 44,894 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,450 |
| African / African-American | 0.00133% | 74,916 |
| European (non-Finnish) | 0.000678% | 147,490 |
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.Pro623=
- Coding
- c.1869C>T
- MANE Select
- NM_014738
- Type
- single nucleotide variant
- Location
- chr17:75492746 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.28 · 7 PDB
Similar variants
- 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
- TMEM94 p.Arg1201Cys 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-pro623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown