ADM p.Leu3=
c.9G>A · rs144409664 · VCV749078
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0657%, 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 5.7 | phastCons 1 |
| Overall | ||
| CADD | 13.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0657%
Middle Eastern · 4/6,084 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.0039%
63/1,613,862 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0657% | 1,521 |
| Admixed American | 0.0283% | 3,530 |
| Finnishnot grpmax-eligible | 0.0094% | 10,639 |
| South Asian | 0.00329% | 30,363 |
| European (non-Finnish) | 0.00271% | 36,875 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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
- ADM
- Protein
- p.Leu3=
- Coding
- c.9G>A
- MANE Select
- NM_001124
- dbSNP
- rs144409664
- Type
- single nucleotide variant
- Location
- chr11:10305709 (GRCh38)
- Gene constraint
- LOEUF 0.581 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 62.35 · 8 PDB
Similar variants
- ADM p.Ser50Arg Benign ★★ same type
- ADM p.Ala22Ser Uncertain significance ★ ⚠ same type
- ADM p.Ala38Ser Uncertain significance ★ ⚠ same type
- ADM p.Ala38Val Uncertain significance ★ ⚠ same type
- ADM p.Ala87Val Uncertain significance ★ ⚠ same type
- ADM p.Arg23Trp Uncertain significance ★ ⚠ same type
- ADM p.Arg89His Uncertain significance ★ ⚠ same type
- ADM p.Arg94Leu 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/adm-p-leu3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown