LMTK3 p.Pro22=
c.66G>A · rs777419321 · VCV716791
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, 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 0.61 | GERP 0.14, phastCons 1 |
| Overall | ||
| CADD | 13.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
Middle Eastern · 5/3,694 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0991%
Overall
0.00739%
103/1,394,124 alleles · rare
exomes 97/1,242,166 · genomes 6/151,958 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.135% | 739 |
| South Asian | 0.13% | 768 |
| Remaining individualsnot grpmax-eligible | 0.0115% | 8,673 |
| East Asian | 0.00857% | 11,673 |
| Admixed American | 0.00271% | 36,902 |
| African / African-American | 0.00148% | 67,458 |
| European (non-Finnish) | 0.000471% | 212,360 |
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
- LMTK3
- Protein
- p.Pro22=
- Coding
- c.66G>A
- MANE Select
- NM_001388485
- dbSNP
- rs777419321
- Type
- single nucleotide variant
- Location
- chr19:48511511 (GRCh38)
- Gene constraint
- LOEUF 0.517 · pLI 0.89 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.17 · 1 PDB
Similar variants
- LMTK3 p.Leu314= Benign ★★ same type
- LMTK3 p.Leu354= Benign ★★ same type
- LMTK3 c.-35G>T Uncertain significance ★ same type
- LMTK3 c.-44G>A Uncertain significance ★ same type
- LMTK3 c.-45C>T Uncertain significance ★ same type
- LMTK3 c.-6G>T Uncertain significance ★ same type
- LMTK3 p.Ala1040Asp Uncertain significance ★ ⚠ same type
- LMTK3 p.Ala1055Thr 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/lmtk3-p-pro22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown