Is COL4A3 p.Pro176= (c.528A>C) pathogenic?

COL4A3 p.Pro176= (c.528A>C) is classified Uncertain significance in COL4A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Absent from gnomAD v4.1; Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro176= (c.528A>C)?

COL4A3 p.Pro176= (c.528A>C) is associated with autosomal dominant Alport syndrome, Alport syndrome 3b, autosomal recessive, hematuria, benign familial, 2 (ClinVar).

How common is COL4A3 p.Pro176= (c.528A>C) in the general population?

COL4A3 p.Pro176= (c.528A>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.Pro176=

c.528A>C · VCV3585979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal dominant Alport syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.12	GERP -2.3, phastCons 0.12
Overall
CADD	6.981	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.Pro176=
Coding: c.528A>C
MANE Select: NM_000091
Type: single nucleotide variant
Location: chr2:227248502 (GRCh38)

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

Disease context

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

Also linked: Alport syndrome 3b, autosomal recessive hematuria, benign familial, 2

For Alport syndrome (Orphanet):

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

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-pro176 (accessed [today's date]).

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