ERBB2 p.Ala644=
c.1932C>T · rs141678288 · VCV1165633
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.192%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -4.3 |
| Overall | ||
| CADD | 0.369 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.192%
Admixed American · 115/60,022 alleles
Filtering AF
0.163%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.152%
Overall
0.0122%
197/1,614,166 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.192% | 522 |
| Middle Eastern | 0.0165% | 6,062 |
| East Asian | 0.0111% | 8,977 |
| European (non-Finnish) | 0.00593% | 16,857 |
| South Asian | 0.00329% | 30,361 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| African / African-American | 0.00133% | 75,036 |
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.Ala644=
- Coding
- c.1932C>T
- MANE Select
- NM_004448
- dbSNP
- rs141678288
- Type
- single nucleotide variant
- Location
- chr17:39719820 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 74.65 · 63 PDB
Similar variants
- ERBB2 p.Ala644Thr Uncertain significance ★★ ⚠ same residue
- ERBB2 p.Ala598Asp 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
- ERBB2 p.Arg217Cys 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-ala644 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown