ERBB2 p.Ala115=
c.345C>T · rs200102353 · VCV737080
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.274%, 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 -8 | GERP -5.4 |
| Overall | ||
| CADD | 5.989 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.274%
South Asian · 250/91,084 alleles
Filtering AF
0.247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.236%
Overall
0.0477%
770/1,614,210 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.274% | 364 |
| European (non-Finnish) | 0.0386% | 2,588 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| Middle Eastern | 0.033% | 3,031 |
| Finnishnot grpmax-eligible | 0.0328% | 3,050 |
| Admixed American | 0.0233% | 4,288 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
| East Asian | 0.00446% | 22,441 |
| African / African-American | 0.00266% | 37,529 |
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.Ala115=
- Coding
- c.345C>T
- MANE Select
- NM_004448
- dbSNP
- rs200102353
- Type
- single nucleotide variant
- Location
- chr17:39708440 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 74.65 · 63 PDB
- Residue 115
- a β-strand
Similar variants
- ERBB2 p.Ala115Thr 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-ala115 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown