Is VCAN p.Pro979= (c.2937C>T) pathogenic?

VCAN p.Pro979= (c.2937C>T) is classified Uncertain significance in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0165%, mid); Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Pro979= (c.2937C>T)?

VCAN p.Pro979= (c.2937C>T) is associated with vitreoretinal degeneration (ClinVar).

How common is VCAN p.Pro979= (c.2937C>T) in the general population?

VCAN p.Pro979= (c.2937C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

VCAN p.Pro979=

c.2937C>T · rs886060819 · VCV354409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, 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 0.027	GERP 1.6, phastCons 0.69
Overall
CADD	6.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,036 alleles · ultra-rare exomes 4/1,461,746 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.000254%	393,306

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.Pro979=
Coding: c.2937C>T
MANE Select: NM_004385
dbSNP: rs886060819
Type: single nucleotide variant
Location: chr5:83521243 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 979: the 'gag-alpha (glucosaminoglycan attachment domain)' 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-pro979 (accessed [today's date]).

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