Is ERF p.Arg483His (c.1448G>A) pathogenic?

ERF p.Arg483His (c.1448G>A) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-28). AlphaMissense: likely pathogenic (0.804); Very rare (popmax 0.000256%, nfe); Associated with multiple congenital anomalies/dysmorphic syndrome.

What condition is associated with ERF p.Arg483His (c.1448G>A)?

ERF p.Arg483His (c.1448G>A) is associated with multiple congenital anomalies/dysmorphic syndrome (ClinVar).

How common is ERF p.Arg483His (c.1448G>A) in the general population?

ERF p.Arg483His (c.1448G>A) is very rare (popmax 0.000256%, nfe) (gnomAD).

What do computational predictors say about ERF p.Arg483His (c.1448G>A)?

AlphaMissense predicts likely pathogenic (score 0.804) — an in-silico prediction, not a clinical call.

ERF p.Arg483His

c.1448G>A · VCV4074820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple congenital anomalies/dysmorphic syndrome

Computational evidence

Protein change
AlphaMissense	0.804	likely pathogenic
REVEL	0.256	benign-leaning
SaProt	LLR -8.47	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 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	29.0	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 0.000256% European (non-Finnish) · 3/1,173,236 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000207% 3/1,452,052 alleles · very rare

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: ERF
Protein: p.Arg483His
Coding: c.1448G>A
MANE Select: NM_006494
Type: single nucleotide variant
Location: chr19:42248664 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB

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

Disease context

multiple congenital anomalies/dysmorphic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERF p.Arg183Ter Pathogenic ★★ same type
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same type
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same type
ERF p.Arg233Ter Pathogenic ★★ same type
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same type
ERF p.Gln263Ter Pathogenic ★★ same type
ERF p.Gly53Arg Likely pathogenic ★★ same type
ERF p.Ser24Ter Pathogenic/Likely pathogenic ★★ 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/erf-p-arg483his (accessed [today's date]).

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