COMP p.Ala624=
c.1872G>A · rs200802161 · VCV738701
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.129%, 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 -2.8 | GERP -4 |
| Overall | ||
| CADD | 7.729 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
African / African-American · 97/74,956 alleles
Filtering AF
0.109%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.101%
Overall
0.00675%
109/1,613,850 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.129% | 773 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,417 |
| Admixed American | 0.005% | 20,001 |
| South Asian | 0.0011% | 91,070 |
| European (non-Finnish) | 0.00017% | 589,960 |
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.Ala624=
- Coding
- c.1872G>A
- MANE Select
- NM_000095
- dbSNP
- rs200802161
- Type
- single nucleotide variant
- Location
- chr19:18784938 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 624
- the tsp c-terminal domain; the 'mediates cell survival and induction of the iap family of survival proteins' region; a disulfide bond
Similar variants
- COMP p.Ala624Val Uncertain significance ★★ ⚠ same residue
- COMP p.Ala624Thr Uncertain significance ★ ⚠ same residue
- COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
- COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asp273Val Likely pathogenic ★★ 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/comp-p-ala624 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown