AMPH p.Ala494=
c.1482G>A · rs756707743 · VCV758131
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.005 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.1 | GERP -3.7 |
| Overall | ||
| CADD | 4.924 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,876 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.0018%
29/1,614,182 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,219 |
| South Asian | 0.00878% | 11,386 |
| Admixed American | 0.00666% | 15,005 |
| Finnishnot grpmax-eligible | 0.00156% | 64,040 |
| African / African-American | 0.00133% | 75,054 |
| European (non-Finnish) | 0.000932% | 107,275 |
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.Ala494=
- Coding
- c.1482G>A
- MANE Select
- NM_001635
- dbSNP
- rs756707743
- Type
- single nucleotide variant
- Location
- chr7:38394131 (GRCh38)
- Gene constraint
- LOEUF 0.697 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.84 · 6 PDB
- Residue 494
- the 'disordered' region
Similar variants
- AMPH p.Ala494Val 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.Ala284Val 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-ala494 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown