ERBB3 p.Thr48=
c.144A>T · VCV4917171
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -9 | GERP -3.7 |
| Overall | ||
| CADD | 0.309 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.00062%
10/1,613,948 alleles · ultra-rare
exomes 8/1,461,866 · genomes 2/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| European (non-Finnish) | 0.000763% | 131,112 |
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.Thr48=
- Coding
- c.144A>T
- MANE Select
- NM_001982
- Type
- single nucleotide variant
- Location
- chr12:56083812 (GRCh38)
- Gene constraint
- LOEUF 0.695 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.90 · 23 PDB
- Residue 48
- an α-helix
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-thr48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown