ATP7B p.Ser391Pro
c.1171T>C · rs755785474 · VCV2157025
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5509 | ambiguous |
|---|---|---|
| REVEL | 0.376 | indeterminate |
| SaProt | LLR -12.53 | damaging |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -3.8, phastCons 0.35 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 77 kb · p 0.92 · regional, not allelic |
| Overall | ||
| CADD | 15.17 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 11,999 |
| African / African-American | 0.004% | 24,973 |
| European (non-Finnish) | 0.000678% | 147,506 |
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
- ATP7B
- Protein
- p.Ser391Pro
- Coding
- c.1171T>C
- MANE Select
- NM_000053
- dbSNP
- rs755785474
- Type
- single nucleotide variant
- Location
- chr13:51974049 (GRCh38)
- Gene constraint
- LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.83 · 13 PDB
- Residue 391
- the hma 4 domain; a β-strand
Disease context
Wilson disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Wilson disease (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood, Elderly
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- ATP7B p.Ser391Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- ATP7B p.Ser391= Likely benign ★ same residue
- ATP7B p.Ser391fs Pathogenic/Likely pathogenic ★★ same residue
- ATP7B c.1285+2T>A Pathogenic/Likely pathogenic ★★ same condition
- ATP7B c.1286-2A>G Pathogenic ★★ same condition
- ATP7B c.1543+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ATP7B c.1543+1G>C Pathogenic ★★ same condition
- ATP7B c.1544-2A>G 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/atp7b-p-ser391pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown