Is COL4A4 p.Asp191fs (c.567_568del) pathogenic?

COL4A4 p.Asp191fs (c.567568del) is classified Pathogenic in COL4A4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-29). Absent from gnomAD; Associated with autosomal recessive Alport syndrome.

What condition is associated with COL4A4 p.Asp191fs (c.567_568del)?

COL4A4 p.Asp191fs (c.567_568del) is associated with autosomal recessive Alport syndrome (ClinVar).

How common is COL4A4 p.Asp191fs (c.567_568del) in the general population?

COL4A4 p.Asp191fs (c.567_568del) is absent from gnomAD (gnomAD).

How is Alport syndrome inherited?

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

COL4A4 p.Asp191fs

c.567_568del · rs2475886228 · VCV3063841

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive Alport syndrome

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 9 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL4A4
Protein: p.Asp191fs
Coding: c.567_568del
MANE Select: NM_000092
dbSNP: rs2475886228
Type: Microsatellite
Location: chr2:227111704 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 191: the 'triple-helical region' region; the 'disordered' region

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

Disease context

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

For Alport syndrome (Orphanet):

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

Similar variants

COL4A4 p.Ala493fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Arg989_Gly990insTer Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Cys1294fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Gly1213fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.His1013fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Gly161dup Uncertain significance ★★ same condition
COL4A4 c.2164+19_2164+20insTTTTG Likely benign ★★ same condition
COL4A4 p.Leu1554_Ser1555insTer 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-asp191fs (accessed [today's date]).

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