IGSF1 p.Pro604=
c.1812G>A · rs780114018 · VCV1328073
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0785%, amr)
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 -6.2 | GERP -2.9 |
| Overall | ||
| CADD | 8.328 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0785%
Admixed American · 36/45,852 alleles
Filtering AF
0.0582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0513%
Overall
0.0114%
138/1,209,347 alleles · ultra-rare
exomes 121/1,097,236 · genomes 17/112,111 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0785% | 1,274 |
| Middle Eastern | 0.0457% | 2,186 |
| African / African-American | 0.0297% | 3,366 |
| Remaining individualsnot grpmax-eligible | 0.0168% | 5,947 |
| European (non-Finnish) | 0.00827% | 12,087 |
| South Asian | 0.00176% | 56,813 |
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.Pro604=
- Coding
- c.1812G>A
- MANE Select
- NM_001555
- dbSNP
- rs780114018
- Type
- single nucleotide variant
- Location
- chrX:131278690 (GRCh38)
- Structure
- AlphaFold pLDDT 73.64
- Residue 604
- the ig-like c2-type 6 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-pro604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown