Is COL4A4 p.Arg1114fs (c.3321_3339dup) pathogenic?

COL4A4 p.Arg1114fs (c.33213339dup) is classified Pathogenic/Likely pathogenic in COL4A4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-04). Absent from gnomAD; Associated with COL4A4-related disorder.

What condition is associated with COL4A4 p.Arg1114fs (c.3321_3339dup)?

COL4A4 p.Arg1114fs (c.3321_3339dup) is associated with COL4A4-related disorder (ClinVar).

How common is COL4A4 p.Arg1114fs (c.3321_3339dup) in the general population?

COL4A4 p.Arg1114fs (c.3321_3339dup) is absent from gnomAD (gnomAD).

COL4A4 p.Arg1114fs

c.3321_3339dup · rs2473717934 · VCV2834519

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely 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

COL4A4-related disorder

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 36 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.13	GERP -3.3

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.Arg1114fs
Coding: c.3321_3339dup
MANE Select: NM_000092
dbSNP: rs2473717934
Type: Duplication
Location: chr2:227043134 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 1114: the 'triple-helical region' region; the 'disordered' region

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

Disease context

COL4A4-related disorder

Similar variants

COL4A4 p.Ala1546fs Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Pro428_Asp429insTer Pathogenic/Likely pathogenic ★★ same condition
COL4A4 p.Val741fs Pathogenic ★★ same condition
COL4A4 c.114+1dup Likely pathogenic ★ same condition
COL4A4 p.Pro425fs Likely pathogenic ★ same condition
COL4A4 p.Arg1114= Likely benign ★ same residue
COL4A4 p.Ala1502fs Pathogenic same condition
COL4A4 c.1099+1G>A 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-arg1114fs (accessed [today's date]).

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