Is COL4A4 c.2385del pathogenic?

COL4A4 c.2385del is classified Pathogenic/Likely pathogenic in COL4A4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-15). Very rare (popmax 8.47e-05%, nfe); Associated with Alport syndrome.

What condition is associated with COL4A4 c.2385del?

COL4A4 c.2385del is associated with Alport syndrome, hematuria, benign familial, 1, autosomal recessive Alport syndrome (ClinVar).

How common is COL4A4 c.2385del in the general population?

COL4A4 c.2385del is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Alport syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL4A4 c.2385del

rs1975778377 · VCV951931

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.21	GERP -3.7

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,992 alleles

Overall 6.84e-05% 1/1,461,790 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: COL4A4
Coding: c.2385del
MANE Select: NM_000092
dbSNP: rs1975778377
Type: Deletion
Location: chr2:227057599 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB

Full COL4A4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hematuria, benign familial, 1 autosomal recessive Alport syndrome

For Alport syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

COL4A4 c.1321_1369+3del Pathogenic/Likely pathogenic ★★ same condition
COL4A4 c.327+1_327+5del Likely pathogenic ★★ same condition
COL4A4 c.4091-8_4092del Likely pathogenic ★★ same condition
COL4A4 c.914_930+29del Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Ala1573fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Ala793fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Arg830fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Arg877_Gly888del Likely pathogenic ★★ 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/col4a4-c-2385del (accessed [today's date]).

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