PLEKHM2 p.Ile703=
c.2109C>T · rs1172713973 · VCV478076
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
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 2.7 | GERP 0.66, phastCons 1 |
| Overall | ||
| CADD | 12.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,912 alleles
Filtering AF
0.00624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00062%
10/1,613,108 alleles · ultra-rare
exomes 2/1,460,904 · genomes 8/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,324 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,450 |
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.Ile703=
- Coding
- c.2109C>T
- MANE Select
- NM_015164
- dbSNP
- rs1172713973
- Type
- single nucleotide variant
- Location
- chr1:15729830 (GRCh38)
- Gene constraint
- LOEUF 1.086 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.68 · 4 PDB
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-ile703 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown