IQSEC2 p.Pro642=
c.1926G>A · rs782748026 · VCV197718
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.042%, afr)
Conditions
2
Inborn genetic diseases
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 -8.7 | GERP -3.9 |
| Overall | ||
| CADD | 0.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.042%
African / African-American · 24/57,158 alleles
Filtering AF
0.0289%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0246%
Overall
0.00232%
28/1,207,288 alleles · ultra-rare
exomes 13/1,095,349 · genomes 15/111,939 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.042% | 2,382 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,438 |
| European (non-Finnish) | 0.000336% | 297,954 |
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.Pro642=
- Coding
- c.1926G>A
- MANE Select
- NM_001111125
- dbSNP
- rs782748026
- Type
- single nucleotide variant
- Location
- chrX:53250650 (GRCh38)
- Structure
- AlphaFold pLDDT 54.46 · 2 PDB
- Residue 642
- the 'disordered' region
Similar variants
- IQSEC2 p.Pro642Leu Uncertain significance ★★ ⚠ same residue
- IQSEC2 p.Pro642Arg Uncertain significance ★ ⚠ same residue
- IQSEC2 p.Pro642fs Pathogenic ★ same residue
- IQSEC2 c.2459+21C>T Pathogenic ★★ same condition
- IQSEC2 c.2889+1G>A Pathogenic ★★ same condition
- IQSEC2 p.Ala836Val Pathogenic/Likely pathogenic ★★ same condition
- IQSEC2 p.Arg1055Ter Pathogenic ★★ same condition
- IQSEC2 p.Arg1145Ter Pathogenic ★★ same condition
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-pro642 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown