IGSF1 p.Ser861=
c.2583C>T · rs368932840 · VCV2661440
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0438%, 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 -5 |
| Overall | ||
| CADD | 3.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0438%
African / African-American · 25/57,054 alleles
Filtering AF
0.0305%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.026%
Overall
0.00405%
49/1,209,258 alleles · ultra-rare
exomes 29/1,097,680 · genomes 20/111,578 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0438% | 2,282 |
| Remaining individualsnot grpmax-eligible | 0.0105% | 9,517 |
| Admixed American | 0.00438% | 22,855 |
| East Asian | 0.00296% | 33,749 |
| European (non-Finnish) | 0.00179% | 55,928 |
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
- IGSF1
- Protein
- p.Ser861=
- Coding
- c.2583C>T
- MANE Select
- NM_001555
- dbSNP
- rs368932840
- Type
- single nucleotide variant
- Location
- chrX:131276964 (GRCh38)
- Structure
- AlphaFold pLDDT 73.64
- Residue 861
- the ig-like c2-type 8 domain
Similar variants
- IGSF1 p.Ser861Arg Uncertain significance ★ ⚠ same residue
- IGSF1 p.Arg1184Ter Pathogenic ★★ same type
- IGSF1 p.Asp853Gly Uncertain significance ★★ ⚠ same type
- IGSF1 p.Ile1221Thr Uncertain significance ★★ ⚠ same type
- IGSF1 p.Thr1302Ile Uncertain significance ★★ ⚠ same type
- IGSF1 p.Thr1316Ile Uncertain significance ★★ ⚠ same type
- IGSF1 c.2041+24G>A Benign ★★ same type
- IGSF1 c.2042-70G>C Benign ★★ 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/igsf1-p-ser861 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown