IQSEC2 p.Asp414=
c.1242C>T · rs2074440746 · VCV2583080
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00349%, 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 1.7 | GERP 0.015, phastCons 1 |
| Overall | ||
| CADD | 8.569 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00349%
African / African-American · 2/57,290 alleles
Filtering AF
0.000579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000217%
Overall
0.000744%
9/1,209,023 alleles · very rare
exomes 8/1,096,633 · genomes 1/112,390 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00349% | 28,645 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,551 |
| European (non-Finnish) | 0.000671% | 149,088 |
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
- IQSEC2
- Protein
- p.Asp414=
- Coding
- c.1242C>T
- MANE Select
- NM_001111125
- dbSNP
- rs2074440746
- Type
- single nucleotide variant
- Location
- chrX:53254689 (GRCh38)
- Structure
- AlphaFold pLDDT 54.46 · 2 PDB
Similar variants
- IQSEC2 c.2459+21C>T Pathogenic ★★ same type
- IQSEC2 c.2889+1G>A Pathogenic ★★ same type
- IQSEC2 p.Ala836Val Pathogenic/Likely pathogenic ★★ same type
- IQSEC2 p.Arg1055Ter Pathogenic ★★ same type
- IQSEC2 p.Arg1145Ter Pathogenic ★★ same type
- IQSEC2 p.Arg359His Likely pathogenic ★★ same type
- IQSEC2 p.Arg531Ter Pathogenic/Likely pathogenic ★★ same type
- IQSEC2 p.Arg758Ter Pathogenic ★★ 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/iqsec2-p-asp414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown