IGSF10 p.Lys623=
c.1869A>G · rs143231887 · VCV721049
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.204%, nfe)
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 -1 | GERP -4.2 |
| Overall | ||
| CADD | 1.986 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.204%
European (non-Finnish) · 2,413/1,180,004 alleles
Filtering AF
0.198%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.195%
Overall
0.156%
2,519/1,614,158 alleles · rare
exomes 2,366/1,461,846 · genomes 153/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.204% | 489 |
| Remaining individualsnot grpmax-eligible | 0.0944% | 1,060 |
| African / African-American | 0.024% | 4,169 |
| Finnishnot grpmax-eligible | 0.0234% | 4,270 |
| Admixed American | 0.02% | 5,002 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| East Asian | 0.00223% | 44,876 |
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
- IGSF10
- Protein
- p.Lys623=
- Coding
- c.1869A>G
- MANE Select
- NM_178822
- dbSNP
- rs143231887
- Type
- single nucleotide variant
- Location
- chr3:151448112 (GRCh38)
- Gene constraint
- LOEUF 1.068 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.70
- Residue 623
- the ig-like c2-type 2 domain
Similar variants
- IGSF10 p.Ala1666Gly Uncertain significance ★★ ⚠ same type
- IGSF10 p.Ala1725Thr Uncertain significance ★★ ⚠ same type
- IGSF10 p.Ala275Thr Uncertain significance ★★ ⚠ same type
- IGSF10 p.Arg1484Thr Uncertain significance ★★ ⚠ same type
- IGSF10 p.Arg1684Thr Uncertain significance ★★ ⚠ same type
- IGSF10 p.Arg2403Gln Uncertain significance ★★ ⚠ same type
- IGSF10 p.Arg2410His Uncertain significance ★★ ⚠ same type
- IGSF10 p.Arg2529Gln 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/igsf10-p-lys623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown