Is ERBB2 p.Ser1078= (c.3234C>T) pathogenic?

ERBB2 p.Ser1078= (c.3234C>T) is classified Likely benign in ERBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-20). Very rare (popmax 0.00535%, afr).

How common is ERBB2 p.Ser1078= (c.3234C>T) in the general population?

ERBB2 p.Ser1078= (c.3234C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

ERBB2 p.Ser1078=

c.3234C>T · rs538414026 · VCV2887609

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00535%, 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 -3.2	GERP -4.8
Overall
CADD	0.666	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,830 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00161% 26/1,611,014 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,707
Remaining individualsnot grpmax-eligible	0.00481%	20,775
East Asian	0.00446%	22,420
South Asian	0.0022%	45,391
Admixed American	0.0017%	58,816
European (non-Finnish)	0.00119%	84,214

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.Ser1078=
Coding: c.3234C>T
MANE Select: NM_004448
dbSNP: rs538414026
Type: single nucleotide variant
Location: chr17:39727369 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 1078: a modified residue (phosphoserine); the 'disordered' region

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

Similar variants

ERBB2 p.Ser1078Phe 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-ser1078 (accessed [today's date]).

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