AMN c.1006+27C>T
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00053%, nfe)
Conditions
1
Imerslund-Grasbeck syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +27 | near-intronic (+27 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -0.34 |
| Overall | ||
| CADD | 0.637 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00053%
European (non-Finnish) · 6/1,132,202 alleles
Filtering AF
0.000191%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000125%
Overall
0.000443%
6/1,353,968 alleles · very rare
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
- AMN
- Coding
- c.1006+27C>T
- MANE Select
- NM_030943
- dbSNP
- rs1891303354
- Type
- single nucleotide variant
- Location
- chr14:102930113 (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 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
- AMN c.296-3C>T Uncertain significance ★★ 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-c-1006-plus-27c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown