PML p.Ala675=
c.2025C>T · rs61751123 · VCV776930
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.2%, 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 0.5 | GERP 0.98, phastCons 0.99 |
| Overall | ||
| CADD | 7.334 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.2%
African / African-American · 2,404/75,068 alleles
Filtering AF
3.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.05%
Overall
1.21%
19,477/1,614,222 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.2% | 31 |
| European (non-Finnish) | 1.28% | 78 |
| Remaining individualsnot grpmax-eligible | 1.18% | 85 |
| Ashkenazi Jewishnot grpmax-eligible | 1.01% | 99 |
| Admixed American | 0.893% | 112 |
| Middle Eastern | 0.396% | 252 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| South Asian | 0.233% | 430 |
| Finnishnot grpmax-eligible | 0.222% | 451 |
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
- PML
- Protein
- p.Ala675=
- Coding
- c.2025C>T
- MANE Select
- NM_033238
- dbSNP
- rs61751123
- Type
- single nucleotide variant
- Location
- chr15:74044384 (GRCh38)
- Gene constraint
- LOEUF 0.613 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 71.17 · 20 PDB
Similar variants
- PML c.1710+1245A>G Benign ★★ same type
- PML c.1710+1270G>T Benign ★★ same type
- PML c.1710+1705A>G Benign ★★ same type
- PML c.1710+813G>A Benign ★★ same type
- PML p.Pro761= Benign ★★ same type
- PML p.Pro791= Benign/Likely benign ★★ same type
- PML c.1710+1152C>T Uncertain significance ★ same type
- PML c.1710+98G>A 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/pml-p-ala675 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown