TMLHE p.Asp231=
c.693C>T · rs2520805728 · VCV2429077
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00219%, amr)
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 1 | GERP 0.71, phastCons 1 |
| Overall | ||
| CADD | 3.275 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00219%
Admixed American · 1/45,711 alleles
Overall
8.33e-05%
1/1,200,467 alleles · very rare
exomes 1/1,087,000 · genomes 0/113,467 · joint denominator
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.Asp231=
- Coding
- c.693C>T
- MANE Select
- NM_018196
- dbSNP
- rs2520805728
- Type
- single nucleotide variant
- Location
- chrX:155511738 (GRCh38)
- Structure
- AlphaFold pLDDT 89.10
Similar variants
- TMLHE p.Asp231Val Uncertain significance ★ ⚠ same residue
- 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
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-asp231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown