ERC2 p.Arg415=
c.1245C>T · rs186918021 · VCV2653906
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.06%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.065 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.8 | GERP -4.3 |
| Overall | ||
| CADD | 1.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.06%
Middle Eastern · 64/6,052 alleles
Filtering AF
0.85%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.774%
Overall
0.209%
3,373/1,613,188 alleles · low-frequency
exomes 3,087/1,461,116 · genomes 286/152,072 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.06% | 95 |
| Finnishnot grpmax-eligible | 0.474% | 211 |
| Ashkenazi Jewishnot grpmax-eligible | 0.375% | 267 |
| Remaining individualsnot grpmax-eligible | 0.269% | 372 |
| European (non-Finnish) | 0.217% | 462 |
| Admixed American | 0.128% | 778 |
| South Asian | 0.067% | 1,492 |
| African / African-American | 0.0454% | 2,204 |
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
- ERC2
- Protein
- p.Arg415=
- Coding
- c.1245C>T
- MANE Select
- NM_015576
- dbSNP
- rs186918021
- Type
- single nucleotide variant
- Location
- chr3:56149037 (GRCh38)
- Gene constraint
- LOEUF 0.476 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 74.26
Similar variants
- ERC2 p.Ala105Ser Uncertain significance ★ ⚠ same type
- ERC2 p.Ala107Thr Uncertain significance ★ ⚠ same type
- ERC2 p.Ala202Val Uncertain significance ★ ⚠ same type
- ERC2 p.Ala251Val Uncertain significance ★ ⚠ same type
- ERC2 p.Ala333Ser Uncertain significance ★ ⚠ same type
- ERC2 p.Ala371Pro Uncertain significance ★ ⚠ same type
- ERC2 p.Ala724Thr Uncertain significance ★ ⚠ same type
- ERC2 p.Ala835Thr 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/erc2-p-arg415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown