CD177 p.Ala281Asp
c.842C>A · VCV4222609
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000178%, nfe)
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 -3.3 | GERP -2.6 |
| Regional constraint | o/e 1.18 | unconstrained · MANE · 8,602 bp · p 3.2e-05 · regional, not allelic |
| Overall | ||
| CADD | 0.203 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000178%
European (non-Finnish) · 2/1,123,052 alleles
Filtering AF
3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000143%
2/1,400,742 alleles · very rare
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
- CD177
- Protein
- p.Ala281Asp
- Coding
- c.842C>A
- MANE Select
- NM_020406
- Type
- single nucleotide variant
- Location
- chr19:43361224 (GRCh38)
- Gene constraint
- LOEUF 1.557 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.67 · 2 PDB
Similar variants
- CD177 p.Gly431Arg Benign ★★ same type
- CD177 p.Lys366Arg Benign ★★ same type
- CD177 p.Phe208Val Benign ★★ same type
- CD177 p.Ser364Thr Benign ★★ same type
- CD177 p.Thr210Ile Benign/Likely benign ★★ same type
- CD177 p.Ala3Val Uncertain significance ★ same type
- CD177 p.Ala425Pro Uncertain significance ★ same type
- CD177 p.Arg213Gln 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/cd177-p-ala281asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown