Is COL4A3 p.Pro1109= (c.3327T>C) pathogenic?

COL4A3 p.Pro1109= (c.3327T>C) is classified Likely benign in COL4A3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-14). Absent from gnomAD v4.1; Associated with Alport syndrome.

What condition is associated with COL4A3 p.Pro1109= (c.3327T>C)?

COL4A3 p.Pro1109= (c.3327T>C) is associated with Alport syndrome (ClinVar).

How common is COL4A3 p.Pro1109= (c.3327T>C) in the general population?

COL4A3 p.Pro1109= (c.3327T>C) is absent from gnomAD v4.1 (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Pro1109=

c.3327T>C · rs2469850424 · VCV2970125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP -2.9, phastCons 0.014
Overall
CADD	5.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL4A3
Protein: p.Pro1109=
Coding: c.3327T>C
MANE Select: NM_000091
dbSNP: rs2469850424
Type: single nucleotide variant
Location: chr2:227293307 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 48.64 · 2 PDB
Residue 1109: the 'triple-helical region' region; the 'disordered' region

Full COL4A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

COL4A3 p.Pro1109Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A3 p.Pro1109Arg Uncertain significance ★ ⚠ same residue
COL4A3 p.Pro1109Leu Uncertain significance ★ ⚠ same residue
COL4A3 c.1114+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1504+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1927+1G>A 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/col4a3-p-pro1109 (accessed [today's date]).

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