Is ERBB4 p.Ile337Val (c.1009A>G) pathogenic?

ERBB4 p.Ile337Val (c.1009A>G) is classified Uncertain significance in ERBB4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). AlphaMissense: likely benign (0.2213); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ERBB4 p.Ile337Val (c.1009A>G)?

ERBB4 p.Ile337Val (c.1009A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ERBB4 p.Ile337Val (c.1009A>G) in the general population?

ERBB4 p.Ile337Val (c.1009A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERBB4 p.Ile337Val (c.1009A>G)?

AlphaMissense predicts likely benign (score 0.2213) — an in-silico prediction, not a clinical call.

ERBB4 p.Ile337Val

c.1009A>G · rs1184477882 · VCV2610247

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2213 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2213	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 836 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	22.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERBB4
Protein: p.Ile337Val
Coding: c.1009A>G
MANE Select: NM_005235
dbSNP: rs1184477882
Type: single nucleotide variant
Location: chr2:211712165 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 73.17 · 14 PDB

Full ERBB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERBB4 p.Arg393Gln Uncertain significance ★★ ⚠ same condition
ERBB4 p.Gln598Lys Uncertain significance ★★ ⚠ same condition
ERBB4 p.Glu1138Gly Uncertain significance ★★ ⚠ same condition
ERBB4 p.Glu696Ala Uncertain significance ★★ ⚠ same condition
ERBB4 p.Lys291Arg Uncertain significance ★★ ⚠ same condition
ERBB4 p.Lys681Arg Uncertain significance ★★ ⚠ same condition
ERBB4 p.Lys873Thr Uncertain significance ★★ ⚠ same condition
ERBB4 p.Met831Leu 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/erbb4-p-ile337val (accessed [today's date]).

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