Is COL4A4 p.Ser1492fs (c.4473_4474dup) pathogenic?

COL4A4 p.Ser1492fs (c.44734474dup) is classified Pathogenic in COL4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Absent from gnomAD.

How common is COL4A4 p.Ser1492fs (c.4473_4474dup) in the general population?

COL4A4 p.Ser1492fs (c.4473_4474dup) is absent from gnomAD (gnomAD).

COL4A4 p.Ser1492fs

c.4473_4474dup · rs2149743813 · VCV1374552

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 46 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, 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.Ser1492fs
Coding: c.4473_4474dup
MANE Select: NM_000092
dbSNP: rs2149743813
Type: Microsatellite
Location: chr2:227010360 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 1492: the collagen iv nc1 domain; a disulfide bond; a β-strand

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

Similar variants

COL4A4 p.Ala493fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Arg989_Gly990insTer Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Asp191fs Pathogenic ★★ same type
COL4A4 p.Cys1294fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Glu812fs Pathogenic ★★ same type
COL4A4 p.Gly1213fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.His1013fs Pathogenic/Likely pathogenic ★★ same type
COL4A4 p.Leu267_Tyr268insTer 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-ser1492fs (accessed [today's date]).

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