ERBB2 p.Ala710=
c.2130G>A · rs750389304 · VCV1655944
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00996%, sas)
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 -0.38 | GERP -5.4, phastCons 0.21 |
| Overall | ||
| CADD | 12.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00996%
South Asian · 9/90,398 alleles
Filtering AF
0.00517%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00388%
Overall
0.00106%
17/1,609,518 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00996% | 10,044 |
| Admixed American | 0.00507% | 19,720 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,458 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,162 |
| Finnishnot grpmax-eligible | 0.00314% | 31,840 |
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.Ala710=
- Coding
- c.2130G>A
- MANE Select
- NM_004448
- dbSNP
- rs750389304
- Type
- single nucleotide variant
- Location
- chr17:39723582 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 74.65 · 63 PDB
- Residue 710
- a UniProt-annotated variant site (in vscn2; almost complete loss of erbb2 and erbb3 phosphorylation in the presence or in the absence of nrg1 stimulation, suggesting alteration of downstream signaling; does not affect the subcellular localization at the cell membrane)
Similar variants
- ERBB2 p.Ala710Val Pathogenic 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-ala710 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown