PLEKHM2 p.Pro338=
c.1014C>T · VCV3672747
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00412%, afr)
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 -5.9 | GERP -3.6 |
| Overall | ||
| CADD | 0.217 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00412%
African / African-American · 3/72,876 alleles
Filtering AF
0.00109%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000503%
Overall
0.000782%
12/1,534,472 alleles · very rare
exomes 10/1,382,182 · genomes 2/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00412% | 24,292 |
| East Asian | 0.00233% | 42,890 |
| Remaining individualsnot grpmax-eligible | 0.00169% | 59,278 |
| European (non-Finnish) | 0.000613% | 163,160 |
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.Pro338=
- Coding
- c.1014C>T
- MANE Select
- NM_015164
- Type
- single nucleotide variant
- Location
- chr1:15727086 (GRCh38)
- Gene constraint
- LOEUF 1.086 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.68 · 4 PDB
- Residue 338
- the 'disordered' region
Similar variants
- 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
- PLEKHM2 p.Arg1015Gln 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-pro338 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown