Is VGF p.Arg234Pro (c.701G>C) pathogenic?

VGF p.Arg234Pro (c.701G>C) is classified Uncertain significance in VGF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.164); Absent from gnomAD v4.1.

How common is VGF p.Arg234Pro (c.701G>C) in the general population?

VGF p.Arg234Pro (c.701G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VGF p.Arg234Pro (c.701G>C)?

AlphaMissense predicts likely benign (score 0.164) — an in-silico prediction, not a clinical call.

VGF p.Arg234Pro

c.701G>C · VCV4198711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.164 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.164	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.91	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 0.47	GERP -1.6, phastCons 0.078
Regional constraint	o/e 1.02	unconstrained · MANE · 1,338 bp · p 0.54 · regional, not allelic
Overall
CADD	14.41	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

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: VGF
Protein: p.Arg234Pro
Coding: c.701G>C
MANE Select: NM_003378
Type: single nucleotide variant
Location: chr7:101164143 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.87 · 7 PDB
Residue 234: 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-arg234pro (accessed [today's date]).

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