Is COL4A4 p.Arg724fs (c.2168_2169dup) pathogenic?

COL4A4 p.Arg724fs (c.21682169dup) is classified Pathogenic in COL4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-05). Absent from gnomAD.

How common is COL4A4 p.Arg724fs (c.2168_2169dup) in the general population?

COL4A4 p.Arg724fs (c.2168_2169dup) is absent from gnomAD (gnomAD).

COL4A4 p.Arg724fs

c.2168_2169dup · rs2150277252 · VCV1456542

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 28 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 0.95, 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.Arg724fs
Coding: c.2168_2169dup
MANE Select: NM_000092
dbSNP: rs2150277252
Type: Duplication
Location: chr2:227059618 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 724: the 'triple-helical region' region; the 'disordered' region

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

Similar variants

COL4A4 p.Arg724Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A4 p.Arg724His Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A4 p.Ala1546fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Arg1114fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Cys1588fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Gln1105fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Gly226fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Gly388fs Pathogenic ★★ same type

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-arg724fs (accessed [today's date]).

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