LENG8 p.Pro341=
c.1023G>A · rs138334094 · VCV3045258
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.47%, afr)
Conditions
1
LENG8-related disorder
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 -9 | GERP -8.4 |
| Overall | ||
| CADD | 0.028 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.47%
African / African-American · 352/74,872 alleles
Filtering AF
0.43%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.414%
Overall
0.029%
467/1,607,714 alleles · rare
exomes 263/1,455,546 · genomes 204/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.47% | 213 |
| Admixed American | 0.047% | 2,129 |
| Remaining individualsnot grpmax-eligible | 0.045% | 2,223 |
| Middle Eastern | 0.0384% | 2,606 |
| European (non-Finnish) | 0.00475% | 21,049 |
| South Asian | 0.0011% | 90,648 |
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
- LENG8
- Protein
- p.Pro341=
- Coding
- c.1023G>A
- MANE Select
- NM_052925
- dbSNP
- rs138334094
- Type
- single nucleotide variant
- Location
- chr19:54455565 (GRCh38)
- Gene constraint
- LOEUF 0.375 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.38 · 6 PDB
- Residue 341
- the 'disordered' region
Disease context
LENG8-related disorder
Similar variants
- LENG8 c.1732-9C>T Benign same condition
- LENG8 p.Ala597= Likely benign same condition
- LENG8 p.Arg430Cys Benign same condition
- LENG8 p.Arg616= Likely benign same condition
- LENG8 p.Gln85His Benign same condition
- LENG8 p.Gly464= Likely benign same condition
- LENG8 p.His34= Likely benign same condition
- LENG8 p.Ile557Val Benign same condition
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/leng8-p-pro341 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown