POLG p.Pro635=
c.1905G>A · rs550592814 · VCV317330
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, sas)
Conditions
2
POLG-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.4 | GERP -3.5 |
| Overall | ||
| CADD | 2.824 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
South Asian · 123/91,068 alleles
Filtering AF
0.116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.0092%
148/1,608,740 alleles · rare
exomes 139/1,456,478 · genomes 9/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.135% | 740 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,679 |
| European (non-Finnish) | 0.00119% | 84,282 |
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.Pro635=
- Coding
- c.1905G>A
- MANE Select
- NM_002693
- dbSNP
- rs550592814
- Type
- single nucleotide variant
- Location
- chr15:89325494 (GRCh38)
- Gene constraint
- LOEUF 0.847 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.53 · 36 PDB
Similar variants
- POLG p.Pro635Leu 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-pro635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown