ERBB2 p.Glu1247=
c.3741G>A · rs368770921 · VCV1129456
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0469%, eas)
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 2.3 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 4.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0469%
East Asian · 21/44,818 alleles
Filtering AF
0.0313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0263%
Overall
0.0033%
53/1,605,922 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0469% | 2,134 |
| Remaining individualsnot grpmax-eligible | 0.0353% | 2,832 |
| South Asian | 0.0088% | 11,365 |
| European (non-Finnish) | 0.00017% | 588,748 |
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
- ERBB2
- Protein
- p.Glu1247=
- Coding
- c.3741G>A
- MANE Select
- NM_004448
- dbSNP
- rs368770921
- Type
- single nucleotide variant
- Location
- chr17:39728017 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 74.65 · 63 PDB
- Residue 1247
- the 'disordered' region
Similar variants
- ERBB2 p.Glu1247fs Uncertain significance ★ same residue
- ERBB2 p.Ala598Asp Uncertain significance ★★ ⚠ same type
- ERBB2 p.Ala644Thr Uncertain significance ★★ ⚠ same type
- ERBB2 p.Arg1048Cys Uncertain significance ★★ ⚠ same type
- ERBB2 p.Arg188Cys Uncertain significance ★★ ⚠ same type
- ERBB2 p.Arg188His Uncertain significance ★★ ⚠ same type
- ERBB2 p.Arg190Gln Uncertain significance ★★ ⚠ same type
- ERBB2 p.Arg203His 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/erbb2-p-glu1247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown