Is COL4A4 p.Pro1360fs (c.4079del) pathogenic?

COL4A4 p.Pro1360fs (c.4079del) is classified Pathogenic/Likely pathogenic in COL4A4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-02). Very rare (popmax 6.87e-05%); Associated with hematuria, benign familial, 1.

What condition is associated with COL4A4 p.Pro1360fs (c.4079del)?

COL4A4 p.Pro1360fs (c.4079del) is associated with hematuria, benign familial, 1, autosomal recessive Alport syndrome, Alport syndrome (ClinVar).

How common is COL4A4 p.Pro1360fs (c.4079del) in the general population?

COL4A4 p.Pro1360fs (c.4079del) is very rare (popmax 6.87e-05%) (gnomAD).

COL4A4 p.Pro1360fs

c.4079del · rs1967312678 · VCV1985757

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Conditions

hematuria, benign familial, 1

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 42 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.043	GERP 0.86, phastCons 0.9
Overall
CADD	33.0	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 6.87e-05%

Overall 6.87e-05% 1/1,455,018 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.Pro1360fs
Coding: c.4079del
MANE Select: NM_000092
dbSNP: rs1967312678
Type: Deletion
Location: chr2:227027904 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 1360: 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, benign familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive Alport syndrome Alport syndrome

Similar variants

COL4A4 p.Pro1360= Benign ★★ same residue
COL4A4 p.Pro1360Leu Uncertain significance ★ ⚠ same residue
COL4A4 c.1321_1369+3del Pathogenic/Likely pathogenic ★★ same condition
COL4A4 c.2385del 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

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-pro1360fs (accessed [today's date]).

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