DISP1 p.Ser757=
c.2271G>A · rs150671718 · VCV727577
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.235%, 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 -9 | GERP -4.4 |
| Overall | ||
| CADD | 1.718 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.235%
African / African-American · 176/74,980 alleles
Filtering AF
0.206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.195%
Overall
0.0145%
234/1,614,046 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.235% | 426 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00988% | 10,119 |
| Admixed American | 0.00833% | 12,002 |
| East Asian | 0.00223% | 44,872 |
| European (non-Finnish) | 0.00169% | 59,001 |
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
- DISP1
- Protein
- p.Ser757=
- Coding
- c.2271G>A
- MANE Select
- NM_001377229
- dbSNP
- rs150671718
- Type
- single nucleotide variant
- Location
- chr1:223003668 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.21 · 4 PDB
- Residue 757
- a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent); a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent; the orthologous mouse mutation results in severely decreased extracellular release of shh)
Similar variants
- DISP1 p.Ser757Leu Uncertain significance ★ ⚠ same residue
- DISP1 p.Ala1123Thr Uncertain significance ★★ ⚠ same type
- DISP1 p.Ala1204Thr Uncertain significance ★★ ⚠ same type
- DISP1 p.Ala248Val Uncertain significance ★★ ⚠ same type
- DISP1 p.Ala733Val Uncertain significance ★★ ⚠ same type
- DISP1 p.Arg1061His Uncertain significance ★★ ⚠ same type
- DISP1 p.Arg718His Uncertain significance ★★ ⚠ same type
- DISP1 p.Arg763His 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/disp1-p-ser757 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown