POLM p.Val221=
c.663G>A · rs747094200 · VCV2657419
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000678%, nfe)
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 -3.8 | GERP -3.4 |
| Overall | ||
| CADD | 0.541 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000678%
European (non-Finnish) · 8/1,179,932 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000496%
8/1,613,916 alleles · very rare
exomes 7/1,461,680 · genomes 1/152,236 · joint denominator
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
- POLM
- Protein
- p.Val221=
- Coding
- c.663G>A
- MANE Select
- NM_013284
- dbSNP
- rs747094200
- Type
- single nucleotide variant
- Location
- chr7:44078791 (GRCh38)
- Gene constraint
- LOEUF 1.177 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.39 · 129 PDB
Similar variants
- POLM p.Ala183Val Uncertain significance ★ ⚠ same type
- POLM p.Ala384Thr Uncertain significance ★ ⚠ same type
- POLM p.Ala400Gly Uncertain significance ★ ⚠ same type
- POLM p.Ala51Glu Uncertain significance ★ ⚠ same type
- POLM p.Ala61Ser Uncertain significance ★ ⚠ same type
- POLM p.Ala61Val Uncertain significance ★ ⚠ same type
- POLM p.Arg122Cys Uncertain significance ★ ⚠ same type
- POLM p.Arg122Gly 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/polm-p-val221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown