Is ERBB2 p.Asp873= (c.2619C>T) pathogenic?

ERBB2 p.Asp873= (c.2619C>T) is classified Likely benign in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). Ultra-rare (popmax 0.0173%, afr).

How common is ERBB2 p.Asp873= (c.2619C>T) in the general population?

ERBB2 p.Asp873= (c.2619C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

ERBB2 p.Asp873=

c.2619C>T · rs540921632 · VCV1587284

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

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 -13	GERP -5.3
Overall
CADD	0.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/75,000 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00291% 47/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,769
Middle Eastern	0.0165%	6,062
East Asian	0.00891%	11,218
Admixed American	0.00666%	15,006
European (non-Finnish)	0.00203%	49,168
Remaining individualsnot grpmax-eligible	0.0016%	62,496

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.Asp873=
Coding: c.2619C>T
MANE Select: NM_004448
dbSNP: rs540921632
Type: single nucleotide variant
Location: chr17:39725174 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 873: the protein kinase domain

Full ERBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERBB2 p.Asp873Glu 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
ERBB2 p.Arg203His 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-asp873 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown