TMLHE p.Ser164=
c.492G>A · rs200054718 · VCV3047777
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0241%, 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 2.6 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 7.171 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0241%
Admixed American · 11/45,593 alleles
Filtering AF
0.0135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0104%
Overall
0.00447%
54/1,209,240 alleles · ultra-rare
exomes 49/1,097,858 · genomes 5/111,382 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0241% | 4,145 |
| Middle Eastern | 0.023% | 4,346 |
| East Asian | 0.00593% | 16,863 |
| European (non-Finnish) | 0.00413% | 24,187 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,589 |
| South Asian | 0.00176% | 56,771 |
| African / African-American | 0.00175% | 57,098 |
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.Ser164=
- Coding
- c.492G>A
- MANE Select
- NM_018196
- dbSNP
- rs200054718
- Type
- single nucleotide variant
- Location
- chrX:155514132 (GRCh38)
- Structure
- AlphaFold pLDDT 89.10
Similar variants
- TMLHE p.Ser164Leu 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-ser164 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown