ALX4 p.Pro327=
c.981G>A · VCV4797633
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 -10 | GERP -3.6 |
| Overall | ||
| CADD | 5.393 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,042 alleles
Filtering AF
0.00231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00304%
49/1,612,234 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,042 |
| Admixed American | 0.005% | 19,993 |
| African / African-American | 0.004% | 25,011 |
| South Asian | 0.0033% | 30,341 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,219 |
| European (non-Finnish) | 0.00314% | 31,880 |
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
- ALX4
- Protein
- p.Pro327=
- Coding
- c.981G>A
- MANE Select
- NM_021926
- Type
- single nucleotide variant
- Location
- chr11:44265109 (GRCh38)
- Gene constraint
- LOEUF 0.902 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.00 · 4 PDB
Similar variants
- ALX4 p.Arg265Ter Pathogenic ★★ same type
- ALX4 c.*2991G>A Uncertain significance ★★ same type
- ALX4 p.Arg193Gln Uncertain significance ★★ ⚠ same type
- ALX4 p.Arg257His Uncertain significance ★★ ⚠ same type
- ALX4 p.Arg274His Uncertain significance ★★ ⚠ same type
- ALX4 p.Arg388His Uncertain significance ★★ ⚠ same type
- ALX4 p.Asp176Gly Uncertain significance ★★ ⚠ same type
- ALX4 p.Asp206Asn 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/alx4-p-pro327 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown