Is VCAN p.Pro107= (c.321C>T) pathogenic?

VCAN p.Pro107= (c.321C>T) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-20). Very rare (popmax 0.00891%, eas).

How common is VCAN p.Pro107= (c.321C>T) in the general population?

VCAN p.Pro107= (c.321C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

VCAN p.Pro107=

c.321C>T · rs376721995 · VCV1668424

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -4.5
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,874 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00384% 62/1,614,152 alleles · very rare exomes 56/1,461,886 · genomes 6/152,266 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,218
Admixed American	0.00666%	15,006
European (non-Finnish)	0.00424%	23,601
Remaining individualsnot grpmax-eligible	0.0032%	31,255
South Asian	0.0022%	45,539

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.Pro107=
Coding: c.321C>T
MANE Select: NM_004385
dbSNP: rs376721995
Type: single nucleotide variant
Location: chr5:83490348 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 107: the ig-like v-type domain

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

Similar variants

VCAN c.4004-1G>A Pathogenic ★★ same type
VCAN c.4004-2A>C Pathogenic ★★ same type
VCAN c.4004-2A>G Pathogenic ★★ same type
VCAN c.4004-5T>C Pathogenic ★★ same type
VCAN c.9265+1G>C Pathogenic ★★ same type
VCAN c.9266-5G>A Uncertain significance ★★ same type
VCAN c.9493+5G>A Uncertain significance ★★ same type
VCAN c.9493+5G>T Uncertain significance ★★ same type

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-pro107 (accessed [today's date]).

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