PRMT5 p.Leu81=
c.241C>T · rs11538391 · VCV782583
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.7%, afr) — too common for a highly-penetrant pathogenic allele
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 6.6 | GERP 0.39, phastCons 1 |
| Overall | ||
| CADD | 12.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.7%
African / African-American · 7,990/74,910 alleles
Filtering AF
10.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.4%
Overall
0.583%
9,415/1,613,970 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.7% | 9 |
| Middle Eastern | 0.874% | 114 |
| Remaining individualsnot grpmax-eligible | 0.838% | 119 |
| Admixed American | 0.81% | 123 |
| European (non-Finnish) | 0.0289% | 3,460 |
| South Asian | 0.0143% | 7,006 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,402 |
| Finnishnot grpmax-eligible | 0.00625% | 16,004 |
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
- PRMT5
- Protein
- p.Leu81=
- Coding
- c.241C>T
- MANE Select
- NM_006109
- dbSNP
- rs11538391
- Type
- single nucleotide variant
- Location
- chr14:22928200 (GRCh38)
- Gene constraint
- LOEUF 0.272 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 93.68 · 94 PDB
- Residue 81
- an α-helix; the 'tim barrel' region
Similar variants
- PRMT5 p.His143= Benign ★★ same type
- PRMT5 p.Pro125= Benign ★★ same type
- PRMT5 p.Ala552Ser Uncertain significance ★ ⚠ same type
- PRMT5 p.Ala9Gly Uncertain significance ★ ⚠ same type
- PRMT5 p.Arg377Gln Uncertain significance ★ ⚠ same type
- PRMT5 p.Arg384Gln Uncertain significance ★ ⚠ same type
- PRMT5 p.Arg385Gln Uncertain significance ★ ⚠ same type
- PRMT5 p.Arg385Trp 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/prmt5-p-leu81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown