LMX1B p.Phe234=
c.702C>T · rs1369457750 · VCV1946477
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0185%, mid)
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 2.7 | GERP -0.45, phastCons 1 |
| Overall | ||
| CADD | 13.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0185%
Middle Eastern · 1/5,398 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000683%
11/1,610,494 alleles · ultra-rare
exomes 11/1,458,142 · genomes 0/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0185% | 5,398 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,290 |
| European (non-Finnish) | 0.000763% | 130,981 |
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
- LMX1B
- Protein
- p.Phe234=
- Coding
- c.702C>T
- MANE Select
- NM_001174147
- dbSNP
- rs1369457750
- Type
- single nucleotide variant
- Location
- chr9:126693284 (GRCh38)
- Gene constraint
- LOEUF 0.409 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 70.79
- Residue 234
- a DNA-binding region
Similar variants
- LMX1B c.741+1G>A Pathogenic ★★ same type
- LMX1B c.819+1G>A Pathogenic ★★ same type
- LMX1B p.Ala236Pro Pathogenic ★★ same type
- LMX1B p.Arg221Ter Pathogenic ★★ same type
- LMX1B p.Arg223Gln Pathogenic ★★ same type
- LMX1B p.Arg223Trp Pathogenic/Likely pathogenic ★★ same type
- LMX1B p.Arg231Ter Pathogenic/Likely pathogenic ★★ same type
- LMX1B p.Arg246Gln Pathogenic ★★ 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/lmx1b-p-phe234 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown