ERBB3 p.Thr618=
c.1854C>G · VCV4692806
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 0.19 | GERP -3.7, phastCons 0.97 |
| Overall | ||
| CADD | 6.329 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,896 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.00105%
17/1,613,718 alleles · ultra-rare
exomes 15/1,461,664 · genomes 2/152,054 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,979 |
| South Asian | 0.011% | 9,105 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
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.Thr618=
- Coding
- c.1854C>G
- MANE Select
- NM_001982
- Type
- single nucleotide variant
- Location
- chr12:56094551 (GRCh38)
- Gene constraint
- LOEUF 0.695 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.90 · 23 PDB
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-thr618 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown