Is ERBB2 p.Arg143Gln (c.428G>A) pathogenic?

ERBB2 p.Arg143Gln (c.428G>A) is classified Benign/Likely benign in ERBB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0896); Low-frequency (popmax 1.16%, eas).

How common is ERBB2 p.Arg143Gln (c.428G>A) in the general population?

ERBB2 p.Arg143Gln (c.428G>A) is low-frequency (popmax 1.16%, eas) (gnomAD).

What do computational predictors say about ERBB2 p.Arg143Gln (c.428G>A)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

ERBB2 p.Arg143Gln

c.428G>A · rs185670819 · VCV134090

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.16%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.37	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 16 kb · p 1.3e-16 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.16% East Asian · 519/44,878 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0348% 561/1,613,836 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.16%	86
Remaining individualsnot grpmax-eligible	0.016%	6,249
South Asian	0.00769%	13,010
European (non-Finnish)	0.00195%	51,295
Admixed American	0.00167%	60,008
African / African-American	0.00133%	75,016

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.Arg143Gln
Coding: c.428G>A
MANE Select: NM_004448
dbSNP: rs185670819
Type: single nucleotide variant
Location: chr17:39708523 (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-p-arg143gln (accessed [today's date]).

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