Is VCAN p.Pro1424= (c.4272A>G) pathogenic?

VCAN p.Pro1424= (c.4272A>G) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-04). Rare (popmax 0.131%, afr); Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Pro1424= (c.4272A>G)?

VCAN p.Pro1424= (c.4272A>G) is associated with vitreoretinal degeneration (ClinVar).

How common is VCAN p.Pro1424= (c.4272A>G) in the general population?

VCAN p.Pro1424= (c.4272A>G) is rare (popmax 0.131%, afr) (gnomAD).

VCAN p.Pro1424=

c.4272A>G · rs150960939 · VCV354423

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.131%, afr)

Conditions

vitreoretinal degeneration

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 -1.6	GERP -5.4
Overall
CADD	4.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% African / African-American · 98/75,038 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00632% 102/1,614,016 alleles · rare exomes 44/1,461,704 · genomes 58/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.131%	766
Admixed American	0.00334%	29,976
Remaining individualsnot grpmax-eligible	0.0032%	31,246

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.Pro1424=
Coding: c.4272A>G
MANE Select: NM_004385
dbSNP: rs150960939
Type: single nucleotide variant
Location: chr5:83537275 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1424: the 'gag-beta' region; the 'disordered' region

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 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
VCAN p.Gly2758Cys Uncertain significance ★★ ⚠ same condition
VCAN p.Gly914Asp Uncertain significance ★★ ⚠ same condition
VCAN p.His1946Tyr 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-pro1424 (accessed [today's date]).

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