LETM1 p.Pro507=
c.1521G>A · rs146433419 · VCV763365
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0298%, nfe)
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 -7.6 | GERP -3 |
| Overall | ||
| CADD | 0.369 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0298%
European (non-Finnish) · 339/1,137,154 alleles
Filtering AF
0.0272%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0262%
Overall
0.0237%
366/1,542,160 alleles · ultra-rare
exomes 334/1,389,826 · genomes 32/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0298% | 3,354 |
| Remaining individualsnot grpmax-eligible | 0.017% | 5,884 |
| South Asian | 0.0109% | 9,142 |
| African / African-American | 0.00691% | 14,466 |
| East Asian | 0.00246% | 40,588 |
| Admixed American | 0.00186% | 53,786 |
| Finnishnot grpmax-eligible | 0.0016% | 62,622 |
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
- LETM1
- Protein
- p.Pro507=
- Coding
- c.1521G>A
- MANE Select
- NM_012318
- dbSNP
- rs146433419
- Type
- single nucleotide variant
- Location
- chr4:1822268 (GRCh38)
- Gene constraint
- LOEUF 0.881 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.36 · 2 PDB
- Residue 507
- the letm1 rbd domain
Similar variants
- LETM1 p.Pro507Leu Uncertain significance ★ ⚠ same residue
- LETM1 p.Ala178Val Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg106His Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg112Cys Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg156Gln Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg307Cys Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg307His Uncertain significance ★★ ⚠ same type
- LETM1 p.Arg323Gln 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/letm1-p-pro507 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown