PLEKHM2 p.Ser17=
c.51G>A · rs370753597 · VCV772520
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 15.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
European (non-Finnish) · 171/1,013,614 alleles
Filtering AF
0.0147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.014%
Overall
0.0136%
177/1,303,116 alleles · ultra-rare
exomes 167/1,152,744 · genomes 10/150,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0169% | 5,928 |
| Remaining individualsnot grpmax-eligible | 0.0109% | 9,215 |
| East Asian | 0.00326% | 30,670 |
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
- PLEKHM2
- Protein
- p.Ser17=
- Coding
- c.51G>A
- MANE Select
- NM_015164
- dbSNP
- rs370753597
- Type
- single nucleotide variant
- Location
- chr1:15684609 (GRCh38)
- Gene constraint
- LOEUF 1.086 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.68 · 4 PDB
- Residue 17
- an α-helix; the 'interaction with kif5b' region
Similar variants
- PLEKHM2 p.Ser17Leu Uncertain significance ★★ ⚠ same residue
- PLEKHM2 p.Ala252Thr Uncertain significance ★★ ⚠ same type
- PLEKHM2 p.Ala277Glu Uncertain significance ★★ ⚠ same type
- PLEKHM2 p.Ala339Thr Uncertain significance ★★ ⚠ same type
- PLEKHM2 p.Ala499Ser Uncertain significance ★★ ⚠ same type
- PLEKHM2 p.Ala689Val Uncertain significance ★★ ⚠ same type
- PLEKHM2 p.Arg1010His Uncertain significance ★★ ⚠ same type
- PLEKHM2 p.Arg1012Gln 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/plekhm2-p-ser17 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown