Is ERF p.Lys512Arg (c.1535A>G) pathogenic?

ERF p.Lys512Arg (c.1535A>G) is classified Uncertain significance in ERF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-31). AlphaMissense: likely benign (0.1031); Very rare (popmax 0.0018%, amr); Associated with ERF-related disorder.

What condition is associated with ERF p.Lys512Arg (c.1535A>G)?

ERF p.Lys512Arg (c.1535A>G) is associated with ERF-related disorder (ClinVar).

How common is ERF p.Lys512Arg (c.1535A>G) in the general population?

ERF p.Lys512Arg (c.1535A>G) is very rare (popmax 0.0018%, amr) (gnomAD).

What do computational predictors say about ERF p.Lys512Arg (c.1535A>G)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

ERF p.Lys512Arg

c.1535A>G · rs2036373009 · VCV3052000

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0018%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERF-related disorder

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -4.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.33	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 0.44, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.0018% Admixed American · 1/55,620 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000316% 5/1,581,284 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0018%	55,620
Remaining individualsnot grpmax-eligible	0.00164%	60,986
African / African-American	0.00136%	73,708
European (non-Finnish)	0.000172%	581,598

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.Lys512Arg
Coding: c.1535A>G
MANE Select: NM_006494
dbSNP: rs2036373009
Type: single nucleotide variant
Location: chr19:42248577 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 512: a cross-link site; the 'disordered' region

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

Disease context

ERF-related disorder

Similar variants

ERF p.Lys512Asn Uncertain significance ★ ⚠ same residue
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg233Ter Pathogenic ★★ same condition
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same condition
ERF p.Gly53Arg Likely pathogenic ★★ same condition
ERF p.Tyr89Cys Pathogenic ★★ same condition
ERF p.Glu35Ter Pathogenic ★ 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-lys512arg (accessed [today's date]).

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