ERBB2 p.Arg351=
c.1051C>A · rs770327076 · VCV1672387
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.34 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.25 | loss · gain 0.01 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 11.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,916 alleles
Overall
0.000206%
3/1,458,268 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,916 |
| South Asian | 0.0011% | 90,964 |
| European (non-Finnish) | 8.48e-05% | 1,178,570 |
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.Arg351=
- Coding
- c.1051C>A
- MANE Select
- NM_004448
- dbSNP
- rs770327076
- Type
- single nucleotide variant
- Location
- chr17:39712351 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 74.65 · 63 PDB
- Residue 351
- a disulfide bond
Similar variants
- ERBB2 p.Arg351Ter 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-arg351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown