AMN p.Leu419=
c.1257G>A · rs2139313588 · VCV1468534
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Imerslund-Grasbeck syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.47 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.57 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.9 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 20.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AMN
- Protein
- p.Leu419=
- Coding
- c.1257G>A
- MANE Select
- NM_030943
- dbSNP
- rs2139313588
- Type
- single nucleotide variant
- Location
- chr14:102930493 (GRCh38)
- Gene constraint
- LOEUF 1.446 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.78 · 1 PDB
Disease context
Imerslund-Grasbeck syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Imerslund-Gräsbeck syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
- Prevalence
- 1-9 / 1 000 000 (Finland)
Similar variants
- AMN p.Leu419fs Pathogenic ★ same residue
- AMN c.208-1G>C Pathogenic/Likely pathogenic ★★ same condition
- AMN c.296-1G>A Likely pathogenic ★★ same condition
- AMN c.44-1G>A Likely pathogenic ★★ same condition
- AMN c.760+1G>A Likely pathogenic ★★ same condition
- AMN c.844-1G>C Likely pathogenic ★★ same condition
- AMN p.Thr41Ile Likely pathogenic ★★ ⚠ same condition
- AMN p.Trp391Ter Pathogenic/Likely pathogenic ★★ 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/amn-p-leu419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown