Is VCAN p.Val2080Phe (c.6238G>T) pathogenic?

VCAN p.Val2080Phe (c.6238G>T) is classified Uncertain significance in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-30). AlphaMissense: likely benign (0.1044); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with VCAN p.Val2080Phe (c.6238G>T)?

VCAN p.Val2080Phe (c.6238G>T) is associated with Inborn genetic diseases (ClinVar).

How common is VCAN p.Val2080Phe (c.6238G>T) in the general population?

VCAN p.Val2080Phe (c.6238G>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about VCAN p.Val2080Phe (c.6238G>T)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

VCAN p.Val2080Phe

c.6238G>T · rs764734647 · VCV1060524

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1044	likely benign
REVEL	0.193	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP -0.075
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	17.51	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,962 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00173% 28/1,614,024 alleles · ultra-rare exomes 23/1,461,742 · genomes 5/152,282 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,662
Remaining individualsnot grpmax-eligible	0.008%	12,502
African / African-American	0.00133%	75,034
European (non-Finnish)	0.0011%	90,766

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.Val2080Phe
Coding: c.6238G>T
MANE Select: NM_004385
dbSNP: rs764734647
Type: single nucleotide variant
Location: chr5:83539241 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2080: the 'gag-beta' 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.Val2080Gly 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
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-val2080phe (accessed [today's date]).

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