Is VCAN p.Pro2344Ser (c.7030C>T) pathogenic?

VCAN p.Pro2344Ser (c.7030C>T) is classified Benign in VCAN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1367); Common (popmax 9.49%, afr) — too common for a highly-penetrant pathogenic allele; Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Pro2344Ser (c.7030C>T)?

VCAN p.Pro2344Ser (c.7030C>T) is associated with vitreoretinal degeneration (ClinVar).

What do computational predictors say about VCAN p.Pro2344Ser (c.7030C>T)?

AlphaMissense predicts likely benign (score 0.1367) — an in-silico prediction, not a clinical call.

VCAN p.Pro2344Ser

Q: How common is VCAN p.Pro2344Ser (c.7030C>T) in the general population?

VCAN p.Pro2344Ser (c.7030C>T) is common (popmax 9.49%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7030C>T · rs61733401 · VCV354437

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1367 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.49%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

vitreoretinal degeneration

Computational evidence

Protein change
AlphaMissense	0.1367	likely benign
REVEL	0.055	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 0.56	GERP -2.1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	6.345	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 9.49% African / African-American · 7,119/75,008 alleles

Filtering AF 9.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.23%

Overall 0.563% 9,092/1,614,004 alleles · common exomes 4,896/1,461,778 · genomes 4,196/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.49%	11
Middle Eastern	1.14%	88
Admixed American	1.06%	95
Remaining individualsnot grpmax-eligible	0.789%	127
Ashkenazi Jewishnot grpmax-eligible	0.142%	705
European (non-Finnish)	0.0594%	1,683
South Asian	0.0373%	2,679

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.Pro2344Ser
Coding: c.7030C>T
MANE Select: NM_004385
dbSNP: rs61733401
Type: single nucleotide variant
Location: chr5:83540033 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2344: the 'gag-beta' region

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

Disease context

vitreoretinal degeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VCAN p.Pro2344= Likely benign ★ same residue
VCAN c.*905A>G Uncertain significance ★★ same condition
VCAN p.Ala2446Val Uncertain significance ★★ ⚠ same condition
VCAN p.Arg1431His Uncertain significance ★★ ⚠ same condition
VCAN p.Glu2277Lys Uncertain significance ★★ ⚠ same condition
VCAN p.Gly1068Ser Uncertain significance ★★ ⚠ same condition
VCAN p.Gly2758Cys Uncertain significance ★★ ⚠ same condition
VCAN p.Gly914Asp 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-pro2344ser (accessed [today's date]).

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