Is VGF p.Arg419= (c.1257C>G) pathogenic?

VGF p.Arg419= (c.1257C>G) is classified Likely benign in VGF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-22). Rare (popmax 0.269%, amr).

How common is VGF p.Arg419= (c.1257C>G) in the general population?

VGF p.Arg419= (c.1257C>G) is rare (popmax 0.269%, amr) (gnomAD).

VGF p.Arg419=

c.1257C>G · rs367911331 · VCV718872

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.269%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -1, phastCons 1
Overall
CADD	11.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.269% Admixed American · 144/53,482 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.22%

Overall 0.0103% 162/1,570,344 alleles · rare exomes 101/1,418,746 · genomes 61/151,598 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.269%	371
African / African-American	0.00814%	12,285
Remaining individualsnot grpmax-eligible	0.00328%	30,465
European (non-Finnish)	0.000863%	115,871

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: VGF
Protein: p.Arg419=
Coding: c.1257C>G
MANE Select: NM_003378
dbSNP: rs367911331
Type: single nucleotide variant
Location: chr7:101163587 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.87 · 7 PDB
Residue 419: the 'disordered' region

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

Similar variants

VGF p.Arg308= Benign ★★ same type
VGF p.Glu107Gln Benign ★★ same type
VGF p.Leu327= Benign ★★ same type
VGF p.Pro492= Benign/Likely benign ★★ same type
VGF p.Ala149Val Uncertain significance ★ ⚠ same type
VGF p.Ala160Glu Uncertain significance ★ ⚠ same type
VGF p.Ala181Glu Uncertain significance ★ ⚠ same type
VGF p.Ala233Glu 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/vgf-p-arg419 (accessed [today's date]).

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