Is ERBB2 p.Gln393= (c.1179G>A) pathogenic?

ERBB2 p.Gln393= (c.1179G>A) is classified Conflicting classifications of pathogenicity in ERBB2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0706%, afr); Associated with visceral neuropathy, familial, 2, autosomal recessive.

How common is ERBB2 p.Gln393= (c.1179G>A) in the general population?

ERBB2 p.Gln393= (c.1179G>A) is ultra-rare (popmax 0.0706%, afr) (gnomAD).

ERBB2 p.Gln393=

Q: What condition is associated with ERBB2 p.Gln393= (c.1179G>A)?

ERBB2 p.Gln393= (c.1179G>A) is associated with visceral neuropathy, familial, 2, autosomal recessive, gastric cancer, ovarian cancer (ClinVar).

c.1179G>A · rs147204600 · VCV1587981

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0706%, afr)

Conditions

visceral neuropathy, familial, 2, autosomal recessive

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 4	GERP -1.9, phastCons 1
Overall
CADD	2.474	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0706% African / African-American · 53/75,042 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.00359% 58/1,614,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0706%	1,416
Admixed American	0.00333%	30,009
Remaining individualsnot grpmax-eligible	0.0032%	31,247
European (non-Finnish)	8.47e-05%	1,179,942

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.Gln393=
Coding: c.1179G>A
MANE Select: NM_004448
dbSNP: rs147204600
Type: single nucleotide variant
Location: chr17:39715316 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 63 PDB
Residue 393: an α-helix

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

Disease context

visceral neuropathy, familial, 2, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastric cancer ovarian cancer lung cancer glioma susceptibility 1

Similar variants

ERBB2 p.Ala598Asp Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg1048Cys Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg188Cys Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg190Gln Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg203His Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg217Cys Uncertain significance ★★ ⚠ same condition
ERBB2 p.Arg517Gln Uncertain significance ★★ ⚠ same condition
ERBB2 p.Asp1084Tyr Uncertain significance ★★ ⚠ same condition

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-gln393 (accessed [today's date]).

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