Is COL4A4 p.Pro573fs (c.1716del) pathogenic?

COL4A4 p.Pro573fs (c.1716del) is classified Pathogenic in COL4A4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-07-20). Very rare (popmax 8.47e-05%, nfe); Associated with Hematuria.

What condition is associated with COL4A4 p.Pro573fs (c.1716del)?

COL4A4 p.Pro573fs (c.1716del) is associated with Hematuria, Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A4 p.Pro573fs (c.1716del) in the general population?

COL4A4 p.Pro573fs (c.1716del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

COL4A4 p.Pro573fs

c.1716del · rs772659513 · VCV1963410

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

Conditions

Hematuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 24 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 0.95, phastCons 1
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 0.000657% 1/152,096 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
Protein: p.Pro573fs
Coding: c.1716del
MANE Select: NM_000092
dbSNP: rs772659513
Type: Deletion
Location: chr2:227080530 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 573: the 'triple-helical region' region; the 'disordered' region

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

Disease context

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

Also linked: Alport syndrome hematuria, benign familial

Similar variants

COL4A4 p.Pro573= Conflicting classifications of pathogenicity ★ same residue
COL4A4 c.1321_1369+3del Pathogenic/Likely pathogenic ★★ same condition
COL4A4 c.2385del Pathogenic/Likely pathogenic ★★ same condition
COL4A4 c.71+1del Pathogenic/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

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-p-pro573fs (accessed [today's date]).

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