AMPH p.Ala284=
c.852G>A · rs149933378 · VCV727314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.125%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.037 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.7 |
| Overall | ||
| CADD | 0.732 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.125%
Middle Eastern · 6/4,790 alleles
Filtering AF
0.0545%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0373%
Overall
0.0104%
167/1,602,422 alleles · rare
exomes 148/1,450,174 · genomes 19/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.125% | 798 |
| South Asian | 0.046% | 2,173 |
| Remaining individualsnot grpmax-eligible | 0.0372% | 2,690 |
| Admixed American | 0.0118% | 8,458 |
| European (non-Finnish) | 0.00741% | 13,501 |
| African / African-American | 0.00268% | 37,377 |
| East Asian | 0.00224% | 44,726 |
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
- AMPH
- Protein
- p.Ala284=
- Coding
- c.852G>A
- MANE Select
- NM_001635
- dbSNP
- rs149933378
- Type
- single nucleotide variant
- Location
- chr7:38463011 (GRCh38)
- Gene constraint
- LOEUF 0.697 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.84 · 6 PDB
- Residue 284
- the 'disordered' region
Similar variants
- AMPH p.Ala284Val Uncertain significance ★ ⚠ same residue
- AMPH c.1017+10T>C Likely benign ★★ same type
- AMPH p.Thr586Met Likely benign ★★ same type
- AMPH p.Ala10Thr Uncertain significance ★ ⚠ same type
- AMPH p.Ala169Gly Uncertain significance ★ ⚠ same type
- AMPH p.Ala239Ser Uncertain significance ★ ⚠ same type
- AMPH p.Ala248Val Uncertain significance ★ ⚠ same type
- AMPH p.Ala287Thr 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/amph-p-ala284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown