Is VCAN p.Ala360Pro (c.1078G>C) pathogenic?

VCAN p.Ala360Pro (c.1078G>C) is classified Uncertain significance in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-30). AlphaMissense: likely benign (0.1122); Ultra-rare (popmax 0.0387%, afr); Associated with Inborn genetic diseases.

What condition is associated with VCAN p.Ala360Pro (c.1078G>C)?

VCAN p.Ala360Pro (c.1078G>C) is associated with Inborn genetic diseases (ClinVar).

How common is VCAN p.Ala360Pro (c.1078G>C) in the general population?

VCAN p.Ala360Pro (c.1078G>C) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

What do computational predictors say about VCAN p.Ala360Pro (c.1078G>C)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

VCAN p.Ala360Pro

c.1078G>C · rs374992475 · VCV1002138

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.297	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -4.8, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 29 kb · p 6.4e-09 · regional, not allelic
Overall
CADD	16.58	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 0.0387% African / African-American · 29/74,910 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.0018% 29/1,613,876 alleles · ultra-rare

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.Ala360Pro
Coding: c.1078G>C
MANE Select: NM_004385
dbSNP: rs374992475
Type: single nucleotide variant
Location: chr5:83519384 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 360: the 'gag-alpha (glucosaminoglycan attachment domain)' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VCAN p.Ala360Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
VCAN p.Ala1048Val Uncertain significance ★★ ⚠ same condition
VCAN p.Ala1228Thr Uncertain significance ★★ ⚠ same condition
VCAN p.Ala1314Gly Uncertain significance ★★ same condition
VCAN p.Ala1533Gly Uncertain significance ★★ ⚠ same condition
VCAN p.Ala2446Val Uncertain significance ★★ ⚠ same condition
VCAN p.Ala275Ser Uncertain significance ★★ ⚠ same condition
VCAN p.Ala2772Thr 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-ala360pro (accessed [today's date]).

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