COMP p.Arg738His
c.2213G>A · rs766913050 · VCV891938
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1051 | likely benign |
|---|---|---|
| REVEL | 0.776 | moderately pathogenic-leaning |
| SaProt | LLR -5.50 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -3, phastCons 0.99 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic |
| Overall | ||
| CADD | 29.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.0608% | 1,645 |
| Admixed Americangrpmax | 0.0317% | 3,158 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,680 |
| European (non-Finnish) | 0.0131% | 7,662 |
| African / African-American | 0.00801% | 12,489 |
| East Asian | 0.00446% | 22,445 |
| South Asian | 0.0011% | 91,092 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- COMP
- Protein
- p.Arg738His
- Coding
- c.2213G>A
- MANE Select
- NM_000095
- dbSNP
- rs766913050
- Type
- single nucleotide variant
- Location
- chr19:18783068 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 738
- the tsp c-terminal domain; the 'mediates cell survival and induction of the iap family of survival proteins' region; a β-strand; a disulfide bond
Disease context
pseudoachondroplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: multiple epiphyseal dysplasia type 1
For Pseudoachondroplasia (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- COMP p.Arg738Cys Uncertain significance ★ ⚠ same residue
- COMP p.Arg738= Likely benign ★ same residue
- COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asp273Val Likely pathogenic ★★ same condition
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/comp-p-arg738his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown