ERBB3 p.Ser869=
c.2607T>C · rs541947408 · VCV2643068
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.157%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP 0.79, phastCons 0.001 |
| Overall | ||
| CADD | 9.074 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.157%
South Asian · 143/91,026 alleles
Filtering AF
0.136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.128%
Overall
0.0105%
169/1,612,928 alleles · rare
exomes 158/1,461,094 · genomes 11/151,834 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.157% | 637 |
| Middle Eastern | 0.0736% | 1,359 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,802 |
| Admixed American | 0.00667% | 14,995 |
| European (non-Finnish) | 0.000848% | 117,991 |
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
- ERBB3
- Protein
- p.Ser869=
- Coding
- c.2607T>C
- MANE Select
- NM_001982
- dbSNP
- rs541947408
- Type
- single nucleotide variant
- Location
- chr12:56097931 (GRCh38)
- Gene constraint
- LOEUF 0.695 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.90 · 23 PDB
- Residue 869
- the protein kinase domain
Similar variants
- ERBB3 p.Ile703Leu Uncertain significance ★★ ⚠ same type
- ERBB3 p.Lys747Asn Uncertain significance ★★ ⚠ same type
- ERBB3 p.Pro1142Leu Uncertain significance ★★ ⚠ same type
- ERBB3 p.Pro238Leu Uncertain significance ★★ ⚠ same type
- ERBB3 p.Trp373Arg Uncertain significance ★★ ⚠ same type
- ERBB3 c.1109+202A>G Likely benign ★★ same type
- ERBB3 c.1109+207G>A Benign ★★ same type
- ERBB3 c.1860-128G>A Benign ★★ 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/erbb3-p-ser869 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown