Is VCAN p.Phe2527= (c.7581C>T) pathogenic?

VCAN p.Phe2527= (c.7581C>T) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-18). Rare (popmax 0.379%, mid); Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Phe2527= (c.7581C>T)?

VCAN p.Phe2527= (c.7581C>T) is associated with vitreoretinal degeneration (ClinVar).

How common is VCAN p.Phe2527= (c.7581C>T) in the general population?

VCAN p.Phe2527= (c.7581C>T) is rare (popmax 0.379%, mid) (gnomAD).

VCAN p.Phe2527=

c.7581C>T · rs149880697 · VCV354445

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.379%, mid)

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 -3.9	GERP -5.4
Overall
CADD	0.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.379% Middle Eastern · 23/6,062 alleles

Filtering AF 0.259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.22%

Overall 0.0143% 230/1,613,758 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.379%	264
African / African-American	0.0467%	2,141
Remaining individualsnot grpmax-eligible	0.0272%	3,676
European (non-Finnish)	0.0121%	8,251
Admixed American	0.0117%	8,568
South Asian	0.0033%	30,349
Finnishnot grpmax-eligible	0.00313%	31,983

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.Phe2527=
Coding: c.7581C>T
MANE Select: NM_004385
dbSNP: rs149880697
Type: single nucleotide variant
Location: chr5:83540584 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2527: the 'gag-beta' 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-phe2527 (accessed [today's date]).

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