Is VGF p.Ser284Arg (c.852C>A) pathogenic?

VGF p.Ser284Arg (c.852C>A) is classified Uncertain significance in VGF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: ambiguous (0.3963); Absent from gnomAD v4.1.

How common is VGF p.Ser284Arg (c.852C>A) in the general population?

VGF p.Ser284Arg (c.852C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VGF p.Ser284Arg (c.852C>A)?

AlphaMissense predicts ambiguous (score 0.3963) — an in-silico prediction, not a clinical call.

VGF p.Ser284Arg

c.852C>A · VCV4198713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3963 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,469,904)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3963	ambiguous
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.084, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,338 bp · p 0.54 · regional, not allelic
Overall
CADD	21.2	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

No allele count reported in gnomAD v4.1 (AN 1,469,904). 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: VGF
Protein: p.Ser284Arg
Coding: c.852C>A
MANE Select: NM_003378
Type: single nucleotide variant
Location: chr7:101163992 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.87 · 7 PDB

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-ser284arg (accessed [today's date]).

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