EZR p.Pro474=
c.1422A>T · rs773034103 · VCV435105
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0257%, amr)
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 -20 | GERP -4.2 |
| Overall | ||
| CADD | 0.012 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0257%
Admixed American · 13/50,486 alleles
Filtering AF
0.0204%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0194%
Overall
0.019%
261/1,375,586 alleles · ultra-rare
exomes 221/1,240,898 · genomes 40/134,688 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0257% | 3,884 |
| European (non-Finnish) | 0.0228% | 4,388 |
| Finnishnot grpmax-eligible | 0.0147% | 6,805 |
| Remaining individualsnot grpmax-eligible | 0.0138% | 7,248 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00427% | 23,430 |
| African / African-American | 0.00158% | 63,284 |
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
- EZR
- Protein
- p.Pro474=
- Coding
- c.1422A>T
- MANE Select
- NM_001111077
- dbSNP
- rs773034103
- Type
- single nucleotide variant
- Location
- chr6:158767435 (GRCh38)
- Gene constraint
- LOEUF 0.697 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.16 · 7 PDB
- Residue 474
- the 'interaction with scyl3' region
Similar variants
- EZR p.Ala494Val Uncertain significance ★★ ⚠ same type
- EZR p.Arg381Gln Uncertain significance ★★ ⚠ same type
- EZR p.Thr533Met Uncertain significance ★★ ⚠ same type
- EZR p.Asn251Ser Likely benign ★★ same type
- EZR p.Glu377= Benign/Likely benign ★★ same type
- EZR p.Tyr354= Benign ★★ same type
- EZR c.959+7G>A Conflicting classifications of pathogenicity ★ same type
- EZR p.Ala187Val 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/ezr-p-pro474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown