ENG p.His565=
c.1695T>C · rs750637713 · VCV528084
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, eas)
Conditions
3
Cardiovascular phenotype
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 0.073 | GERP -3.2, phastCons 0.001 |
| Overall | ||
| CADD | 3.011 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,896 alleles
Filtering AF
0.00883%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00136%
22/1,614,062 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,612 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| African / African-American | 0.004% | 24,975 |
| European (non-Finnish) | 0.000593% | 168,576 |
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
- ENG
- Protein
- p.His565=
- Coding
- c.1695T>C
- MANE Select
- NM_001114753
- dbSNP
- rs750637713
- Type
- single nucleotide variant
- Location
- chr9:127817195 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 565
- a β-strand
Similar variants
- ENG p.His565Gln Uncertain significance ★★ ⚠ same residue
- ENG p.His565fs Pathogenic ★ same residue
- ENG p.Arg529His Pathogenic ★★★ ⚠ same condition
- ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same condition
- ENG p.Cys382Tyr Pathogenic ★★★ same condition
- ENG p.Cys549Gly Likely pathogenic ★★★ same condition
- ENG p.Gly331Ser Pathogenic ★★★ ⚠ same condition
- ENG p.Gly603Arg Likely pathogenic ★★★ same condition
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/eng-p-his565 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown