ERBB2 p.Thr1242=
c.3726G>A · rs753222413 · VCV2169609
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 -7.8 | GERP -4.3 |
| Overall | ||
| CADD | 0.088 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,912 alleles
Filtering AF
0.00544%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00474%
Overall
0.00546%
88/1,610,264 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,559 |
| European (non-Finnish) | 0.00636% | 15,723 |
| Finnishnot grpmax-eligible | 0.00326% | 30,655 |
| South Asian | 0.0022% | 45,532 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,434 |
| African / African-American | 0.00133% | 75,004 |
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.Thr1242=
- Coding
- c.3726G>A
- MANE Select
- NM_004448
- dbSNP
- rs753222413
- Type
- single nucleotide variant
- Location
- chr17:39728002 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 74.65 · 63 PDB
- Residue 1242
- the 'disordered' region
Similar variants
- ERBB2 p.Thr1242Lys Uncertain significance ★ ⚠ same residue
- ERBB2 p.Thr1242Met 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
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-thr1242 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown