ATP1B1 p.Pro74=
c.222G>A · rs144621395 · VCV928641
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -4 |
| Overall | ||
| CADD | 5.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
African / African-American · 799/74,984 alleles
Filtering AF
1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.98%
Overall
0.108%
1,746/1,613,208 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.07% | 94 |
| Middle Eastern | 0.33% | 303 |
| Remaining individualsnot grpmax-eligible | 0.178% | 563 |
| Ashkenazi Jewishnot grpmax-eligible | 0.125% | 800 |
| Admixed American | 0.103% | 967 |
| European (non-Finnish) | 0.06% | 1,666 |
| South Asian | 0.0099% | 10,102 |
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
- ATP1B1
- Protein
- p.Pro74=
- Coding
- c.222G>A
- MANE Select
- NM_001677
- dbSNP
- rs144621395
- Type
- single nucleotide variant
- Location
- chr1:169111494 (GRCh38)
- Gene constraint
- LOEUF 0.195 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 89.68 · 27 PDB
Similar variants
- ATP1B1 p.Pro74Leu Uncertain significance ★ ⚠ same residue
- ATP1B1 p.Val261Ile Uncertain significance ★★ ⚠ same type
- ATP1B1 p.Arg107= Benign ★★ same type
- ATP1B1 p.Pro200= Benign/Likely benign ★★ same type
- ATP1B1 p.Tyr279= Benign/Likely benign ★★ same type
- ATP1B1 c.568-20A>C Uncertain significance ★ same type
- ATP1B1 c.97+10G>C Uncertain significance ★ same type
- ATP1B1 p.Ala73Thr 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/atp1b1-p-pro74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown