IGSF1 p.Asp300=
c.900C>T · VCV4804042
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0461%, mid)
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 0.35 | GERP -4.9, phastCons 0.001 |
| Overall | ||
| CADD | 0.562 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0461%
Middle Eastern · 2/4,338 alleles
Filtering AF
0.00815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00405%
Overall
0.00282%
34/1,203,945 alleles · ultra-rare
exomes 26/1,091,497 · genomes 8/112,448 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0461% | 2,169 |
| Remaining individualsnot grpmax-eligible | 0.0148% | 6,770 |
| African / African-American | 0.0122% | 8,184 |
| East Asian | 0.00889% | 11,250 |
| South Asian | 0.00706% | 14,174 |
| Admixed American | 0.00218% | 45,850 |
| European (non-Finnish) | 0.00112% | 88,927 |
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.Asp300=
- Coding
- c.900C>T
- MANE Select
- NM_001555
- Type
- single nucleotide variant
- Location
- chrX:131283032 (GRCh38)
- Structure
- AlphaFold pLDDT 73.64
- Residue 300
- the ig-like c2-type 3 domain
Similar variants
- 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
- IGSF1 c.2896+34G>A 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-asp300 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown