PLEKHM2 p.Pro372=
c.1116C>G · rs567266704 · VCV1548487
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00449%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -2.8 |
| Overall | ||
| CADD | 2.833 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00449%
East Asian · 2/44,580 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000996%
16/1,606,000 alleles · very rare
exomes 11/1,453,760 · genomes 5/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00449% | 22,290 |
| African / African-American | 0.00401% | 24,969 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00342% | 29,282 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,066 |
| South Asian | 0.00222% | 44,976 |
| European (non-Finnish) | 0.00051% | 196,092 |
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.Pro372=
- Coding
- c.1116C>G
- MANE Select
- NM_015164
- dbSNP
- rs567266704
- Type
- single nucleotide variant
- Location
- chr1:15727188 (GRCh38)
- Gene constraint
- LOEUF 1.086 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.68 · 4 PDB
- Residue 372
- the 'disordered' region
Similar variants
- PLEKHM2 p.Pro372Leu Uncertain significance ★★ ⚠ same residue
- PLEKHM2 p.Pro372Arg Uncertain significance ★ ⚠ same residue
- PLEKHM2 p.Pro372His 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
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-pro372 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown