Is ERBB2 p.His470Arg (c.1409A>G) pathogenic?

ERBB2 p.His470Arg (c.1409A>G) is classified Uncertain significance in ERBB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-13). AlphaMissense: likely benign (0.0508); Ultra-rare (popmax 0.0156%, eas); Associated with glioma susceptibility 1.

What condition is associated with ERBB2 p.His470Arg (c.1409A>G)?

ERBB2 p.His470Arg (c.1409A>G) is associated with glioma susceptibility 1, gastric cancer, ovarian cancer (ClinVar).

How common is ERBB2 p.His470Arg (c.1409A>G) in the general population?

ERBB2 p.His470Arg (c.1409A>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ERBB2 p.His470Arg (c.1409A>G)?

AlphaMissense predicts likely benign (score 0.0508) — an in-silico prediction, not a clinical call.

ERBB2 p.His470Arg

c.1409A>G · rs201097345 · VCV1432121

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0508 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glioma susceptibility 1

Computational evidence

Protein change
AlphaMissense	0.0508	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.51	GERP -5.3
Regional constraint	o/e 0.71	unconstrained · MANE · 16 kb · p 1.3e-16 · regional, not allelic
Overall
CADD	1.35	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,878 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00062% 10/1,612,244 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
Finnishnot grpmax-eligible	0.00161%	62,118
European (non-Finnish)	0.000169%	590,009

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.His470Arg
Coding: c.1409A>G
MANE Select: NM_004448
dbSNP: rs201097345
Type: single nucleotide variant
Location: chr17:39715835 (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

Disease context

glioma susceptibility 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastric cancer ovarian cancer lung cancer visceral neuropathy, familial, 2, autosomal recessive

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-his470arg (accessed [today's date]).

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