TMLHE p.Gly266=
c.798T>C · rs782537274 · VCV749213
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.023%, mid)
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 3.5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 9.741 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.023%
Middle Eastern · 1/4,356 alleles
Filtering AF
0.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00932%
Overall
0.00902%
109/1,207,808 alleles · ultra-rare
exomes 102/1,096,386 · genomes 7/111,422 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.023% | 4,356 |
| European (non-Finnish) | 0.0119% | 8,431 |
| Remaining individualsnot grpmax-eligible | 0.00421% | 23,750 |
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
- TMLHE
- Protein
- p.Gly266=
- Coding
- c.798T>C
- MANE Select
- NM_018196
- dbSNP
- rs782537274
- Type
- single nucleotide variant
- Location
- chrX:155507095 (GRCh38)
- Structure
- AlphaFold pLDDT 89.10
Similar variants
- TMLHE p.Arg77Ter Uncertain significance ★★ same type
- TMLHE p.Arg93His Uncertain significance ★★ ⚠ same type
- TMLHE p.Glu175Lys Uncertain significance ★★ ⚠ same type
- TMLHE p.Glu369Asp Uncertain significance ★★ ⚠ same type
- TMLHE p.Pro29Ala Uncertain significance ★★ ⚠ same type
- TMLHE p.Thr265Ile Uncertain significance ★★ ⚠ same type
- TMLHE p.Trp53Ter Uncertain significance ★★ same type
- TMLHE p.Leu111= Likely benign ★★ 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/tmlhe-p-gly266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown