Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 6.69%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.8 | GERP 3.9 |
| Overall | ||
| CADD | 0.582 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.69%
African / African-American · 4,980/74,454 alleles
Filtering AF
6.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.47%
Overall
0.363%
5,750/1,585,370 alleles · common
exomes 2,813/1,433,212 · genomes 2,937/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.69% | 15 |
| Admixed American | 0.474% | 211 |
| Remaining individualsnot grpmax-eligible | 0.46% | 217 |
| Middle Eastern | 0.217% | 462 |
| European (non-Finnish) | 0.0154% | 6,483 |
| South Asian | 0.0122% | 8,221 |
| East Asian | 0.00223% | 44,752 |
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
- IQCE
- Protein
- p.Ser659=
- Coding
- c.1977T>C
- MANE Select
- NM_152558
- dbSNP
- rs6955129
- Type
- single nucleotide variant
- Location
- chr7:2610051 (GRCh38)
- Gene constraint
- LOEUF 1.442 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.36
- Residue 659
- the 'disordered' region
Similar variants
- IQCE p.Ser659Cys Uncertain significance ★ ⚠ same residue
- IQCE p.Lys538Arg Uncertain significance ★★ ⚠ same type
- IQCE p.Asp645= Benign/Likely benign ★★ same type
- IQCE p.Leu277= Benign/Likely benign ★★ same type
- IQCE p.Pro586Ser Likely benign ★★ same type
- IQCE p.Met1Ile Likely pathogenic ★ same type
- IQCE p.Trp498Ter Pathogenic ★ same type
- IQCE p.Tyr255Ter 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/iqce-p-ser659 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown