Is ERBB2 c.3159+13G>A pathogenic?

ERBB2 c.3159+13G>A is classified Benign/Likely benign in ERBB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-21). Rare (popmax 0.219%, afr).

How common is ERBB2 c.3159+13G>A in the general population?

ERBB2 c.3159+13G>A is rare (popmax 0.219%, afr) (gnomAD).

ERBB2 c.3159+13G>A

rs375812051 · VCV1598849

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.219%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +13	near-intronic (+13 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.6
Non-coding constraint	Z 4.27	1 kb window · o/e 0.73 · regional · uncalibrated
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.219% African / African-American · 162/73,948 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.181%

Overall 0.0118% 186/1,574,862 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.219%	456
Admixed American	0.0217%	4,611
Remaining individualsnot grpmax-eligible	0.0132%	7,591
South Asian	0.00117%	85,472
European (non-Finnish)	0.000258%	387,519

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
Coding: c.3159+13G>A
MANE Select: NM_004448
dbSNP: rs375812051
Type: single nucleotide variant
Location: chr17:39727016 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB

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

Similar variants

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
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-c-3159-plus-13g-a (accessed [today's date]).

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