Is VCAN p.Arg3092Pro (c.9275G>C) pathogenic?

VCAN p.Arg3092Pro (c.9275G>C) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-31). AlphaMissense: likely benign (0.2383); Ultra-rare (popmax 0.0869%, eas); Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Arg3092Pro (c.9275G>C)?

VCAN p.Arg3092Pro (c.9275G>C) is associated with vitreoretinal degeneration (ClinVar).

How common is VCAN p.Arg3092Pro (c.9275G>C) in the general population?

VCAN p.Arg3092Pro (c.9275G>C) is ultra-rare (popmax 0.0869%, eas) (gnomAD).

What do computational predictors say about VCAN p.Arg3092Pro (c.9275G>C)?

AlphaMissense predicts likely benign (score 0.2383) — an in-silico prediction, not a clinical call.

VCAN p.Arg3092Pro

c.9275G>C · rs528022086 · VCV354463

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2383 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

Conditions

vitreoretinal degeneration

Computational evidence

Protein change
AlphaMissense	0.2383	likely benign
REVEL	0.291	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.083	GERP -4.1, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	13.38	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0869% East Asian · 39/44,866 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00248% 40/1,613,980 alleles · ultra-rare exomes 33/1,461,706 · genomes 7/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,150
European (non-Finnish)	8.48e-05%	1,179,883

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: VCAN
Protein: p.Arg3092Pro
Coding: c.9275G>C
MANE Select: NM_004385
dbSNP: rs528022086
Type: single nucleotide variant
Location: chr5:83545546 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 3092: the egf-like 1 domain

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

Disease context

vitreoretinal degeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VCAN p.Arg3092Cys Uncertain significance ★★ same residue
VCAN p.Arg3092Leu Uncertain significance ★★ same residue
VCAN p.Arg3092Ser Uncertain significance ★ same residue
VCAN c.*905A>G Uncertain significance ★★ same condition
VCAN p.Ala2446Val Uncertain significance ★★ ⚠ same condition
VCAN p.Arg1431His Uncertain significance ★★ ⚠ same condition
VCAN p.Glu2277Lys Uncertain significance ★★ ⚠ same condition
VCAN p.Gly1068Ser Uncertain significance ★★ ⚠ 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/vcan-p-arg3092pro (accessed [today's date]).

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