Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 48.1%, 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 0.33 | GERP -1.5, phastCons 0.016 |
| Overall | ||
| CADD | 4.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
48.1%
African / African-American · 35,962/74,780 alleles
Filtering AF
47.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 47.5%
Overall
23.9%
385,741/1,613,530 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 48.1% | 2 |
| East Asian | 32.8% | 3 |
| Admixed American | 30.3% | 3 |
| South Asian | 28.7% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 26.7% | 4 |
| Remaining individualsnot grpmax-eligible | 25.1% | 4 |
| Middle Eastern | 22.9% | 4 |
| European (non-Finnish) | 21.6% | 5 |
| Finnishnot grpmax-eligible | 17.2% | 6 |
| Amishnot grpmax-eligible | 12.7% | 8 |
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
- ERMARD
- Protein
- p.Ile539=
- Coding
- c.1617C>T
- MANE Select
- NM_018341
- dbSNP
- rs4716399
- Type
- single nucleotide variant
- Location
- chr6:169776551 (GRCh38)
- Gene constraint
- LOEUF 0.996 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.79
Similar variants
- ERMARD p.Ala474Val Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg367His Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg400Ser Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg537Gln Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg544Cys Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg569Cys Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg571Gln Uncertain significance ★★ ⚠ same type
- ERMARD p.Arg571Trp 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/ermard-p-ile539 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown