Is VCAN p.His19Pro (c.56A>C) pathogenic?

VCAN p.His19Pro (c.56A>C) is classified Uncertain significance in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.2058); Very rare (popmax 0.00136%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VCAN p.His19Pro (c.56A>C)?

VCAN p.His19Pro (c.56A>C) is associated with Inborn genetic diseases (ClinVar).

How common is VCAN p.His19Pro (c.56A>C) in the general population?

VCAN p.His19Pro (c.56A>C) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about VCAN p.His19Pro (c.56A>C)?

AlphaMissense predicts likely benign (score 0.2058) — an in-silico prediction, not a clinical call.

VCAN p.His19Pro

c.56A>C · VCV3814827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2058	likely benign
REVEL	0.313	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 6,912 bp · p 0.48 · regional, not allelic
Overall
CADD	21.7	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 0.00136% European (non-Finnish) · 16/1,179,512 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0011% 16/1,461,076 alleles · very 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.His19Pro
Coding: c.56A>C
MANE Select: NM_004385
Type: single nucleotide variant
Location: chr5:83483574 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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.His19Gln Uncertain significance ★ ⚠ same residue
VCAN p.His19Tyr Uncertain significance ★ ⚠ 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

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-his19pro (accessed [today's date]).

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