POLG p.Pro325=
c.975C>A · rs551973680 · VCV138771
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00669%, nfe)
Conditions
2
Inborn genetic diseases
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 -0.046 | GERP -4.1 |
| Overall | ||
| CADD | 1.189 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
European (non-Finnish) · 79/1,180,040 alleles
Filtering AF
0.00546%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00506%
Overall
0.00539%
87/1,613,614 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00669% | 14,937 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,814 |
| African / African-American | 0.004% | 24,976 |
| East Asian | 0.00223% | 44,900 |
| Admixed American | 0.00167% | 60,006 |
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
- POLG
- Protein
- p.Pro325=
- Coding
- c.975C>A
- MANE Select
- NM_002693
- dbSNP
- rs551973680
- Type
- single nucleotide variant
- Location
- chr15:89328991 (GRCh38)
- Gene constraint
- LOEUF 0.847 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.53 · 36 PDB
- Residue 325
- the 'disordered' region
Similar variants
- POLG p.Pro325Leu Uncertain significance ★ ⚠ same residue
- POLG c.3643+2T>C Pathogenic ★★★ same condition
- POLG p.Ala1105Pro Likely pathogenic ★★★ same condition
- POLG p.Arg1096Cys Likely pathogenic ★★★ same condition
- POLG p.Asp1184Asn Pathogenic ★★★ same condition
- POLG p.Gln1175Ter Likely pathogenic ★★★ same condition
- POLG p.Lys1191Asn Likely pathogenic ★★★ same condition
- POLG c.3483-14T>C Uncertain significance ★★★ 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/polg-p-pro325 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown