LETM1 p.Pro139=
c.417G>A · rs552119847 · VCV2902203
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0527%, sas)
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 -12 | GERP -5 |
| Overall | ||
| CADD | 0.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0527%
South Asian · 48/91,082 alleles
Filtering AF
0.0408%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0366%
Overall
0.00539%
87/1,614,228 alleles · ultra-rare
exomes 81/1,461,884 · genomes 6/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0527% | 1,898 |
| Admixed American | 0.0167% | 6,002 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| African / African-American | 0.004% | 25,019 |
| European (non-Finnish) | 0.00178% | 56,192 |
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.Pro139=
- Coding
- c.417G>A
- MANE Select
- NM_012318
- dbSNP
- rs552119847
- Type
- single nucleotide variant
- Location
- chr4:1841524 (GRCh38)
- Gene constraint
- LOEUF 0.881 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.36 · 2 PDB
Similar variants
- LETM1 p.Pro139Ala Uncertain significance ★ ⚠ same residue
- LETM1 p.Pro139Leu 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
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-pro139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown