Is ERF p.Met478Val (c.1432A>G) pathogenic?

ERF p.Met478Val (c.1432A>G) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.1726); Absent from gnomAD v4.1.

How common is ERF p.Met478Val (c.1432A>G) in the general population?

ERF p.Met478Val (c.1432A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERF p.Met478Val (c.1432A>G)?

AlphaMissense predicts likely benign (score 0.1726) — an in-silico prediction, not a clinical call.

ERF p.Met478Val

c.1432A>G · rs562281233 · VCV2505674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1726 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,852)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1726	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -3.87	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 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	22.2	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

No allele count reported in gnomAD v4.1 (AN 1,608,852). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERF
Protein: p.Met478Val
Coding: c.1432A>G
MANE Select: NM_006494
dbSNP: rs562281233
Type: single nucleotide variant
Location: chr19:42248680 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 478: the 'disordered' region

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

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-met478val (accessed [today's date]).

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