ALX4 p.Cys321=
c.963C>T · rs561018820 · VCV3035610
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0497%, 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 -3.4 | GERP -3.6 |
| Overall | ||
| CADD | 2.384 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0497%
Middle Eastern · 3/6,036 alleles
Filtering AF
0.0135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00981%
158/1,610,666 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0497% | 2,012 |
| Admixed American | 0.0217% | 4,610 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,236 |
| European (non-Finnish) | 0.0102% | 9,820 |
| South Asian | 0.0066% | 15,158 |
| East Asian | 0.00447% | 22,385 |
| Finnishnot grpmax-eligible | 0.00318% | 31,404 |
| African / African-American | 0.00267% | 37,508 |
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.Cys321=
- Coding
- c.963C>T
- MANE Select
- NM_021926
- dbSNP
- rs561018820
- Type
- single nucleotide variant
- Location
- chr11:44265127 (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-cys321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown