Is ERF p.Lys481Glu (c.1441A>G) pathogenic?

ERF p.Lys481Glu (c.1441A>G) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.987); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ERF p.Lys481Glu (c.1441A>G)?

ERF p.Lys481Glu (c.1441A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ERF p.Lys481Glu (c.1441A>G) in the general population?

ERF p.Lys481Glu (c.1441A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERF p.Lys481Glu (c.1441A>G)?

AlphaMissense predicts likely pathogenic (score 0.987) — an in-silico prediction, not a clinical call.

ERF p.Lys481Glu

c.1441A>G · rs2513517836 · VCV3090142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.987	likely pathogenic
REVEL	0.168	moderately benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	25.9	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

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: ERF
Protein: p.Lys481Glu
Coding: c.1441A>G
MANE Select: NM_006494
dbSNP: rs2513517836
Type: single nucleotide variant
Location: chr19:42248671 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 481: a cross-link site

Full ERF 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

ERF p.Lys481Arg Uncertain significance ★ ⚠ same residue
ERF p.Lys481Asn Uncertain significance ★ ⚠ same residue
ERF p.Gln263Ter Pathogenic ★★ same condition
ERF p.Ala462Pro Uncertain significance ★★ ⚠ same condition
ERF p.Arg179His Uncertain significance ★★ ⚠ same condition
ERF p.Arg233Gln Uncertain significance ★★ ⚠ same condition
ERF p.Arg312Gln Uncertain significance ★★ ⚠ same condition
ERF p.Arg546Ter 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/erf-p-lys481glu (accessed [today's date]).

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