Is VCAN p.Val1601Phe (c.4801G>T) pathogenic?

VCAN p.Val1601Phe (c.4801G>T) is classified Uncertain significance in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-27). AlphaMissense: likely benign (0.1061); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with VCAN p.Val1601Phe (c.4801G>T)?

VCAN p.Val1601Phe (c.4801G>T) is associated with Inborn genetic diseases (ClinVar).

How common is VCAN p.Val1601Phe (c.4801G>T) in the general population?

VCAN p.Val1601Phe (c.4801G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about VCAN p.Val1601Phe (c.4801G>T)?

AlphaMissense predicts likely benign (score 0.1061) — an in-silico prediction, not a clinical call.

VCAN p.Val1601Phe

c.4801G>T · rs1456341938 · VCV2869746

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1061 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1061	likely benign
REVEL	0.042	moderately 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 -0.33	GERP -5.4
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	0.256	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 0.00534% African / African-American · 4/74,930 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,613,904 alleles · very rare exomes 3/1,461,744 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	8.48e-05%	1,179,938

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.Val1601Phe
Coding: c.4801G>T
MANE Select: NM_004385
dbSNP: rs1456341938
Type: single nucleotide variant
Location: chr5:83537804 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1601: 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.Val1601Ala 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-val1601phe (accessed [today's date]).

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