Is ERICH3 p.Arg1480Pro (c.4439G>C) pathogenic?

ERICH3 p.Arg1480Pro (c.4439G>C) is classified Uncertain significance in ERICH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1339); Absent from gnomAD v4.1.

How common is ERICH3 p.Arg1480Pro (c.4439G>C) in the general population?

ERICH3 p.Arg1480Pro (c.4439G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERICH3 p.Arg1480Pro (c.4439G>C)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

ERICH3 p.Arg1480Pro

c.4439G>C · VCV4665151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.59	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 -0.57	GERP -3.4
Regional constraint	o/e 1.13	unconstrained · MANE · 102 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	1.296	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: ERICH3
Protein: p.Arg1480Pro
Coding: c.4439G>C
MANE Select: NM_001002912
Type: single nucleotide variant
Location: chr1:74571271 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.25
Residue 1480: the 'disordered' region

Full ERICH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERICH3 p.Arg1480Gln Likely benign ★ same residue
ERICH3 p.Ala1022Gly Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1083Glu Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1100Val Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1117Ser Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1185Val Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1215Ser Uncertain significance ★ ⚠ same type
ERICH3 p.Ala1218Thr 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/erich3-p-arg1480pro (accessed [today's date]).

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