Is COL4A3 p.Pro1197= (c.3591A>G) pathogenic?

COL4A3 p.Pro1197= (c.3591A>G) is classified Conflicting classifications of pathogenicity in COL4A3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-07-28). Ultra-rare (popmax 0.0167%, mid); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro1197= (c.3591A>G)?

COL4A3 p.Pro1197= (c.3591A>G) is associated with autosomal dominant Alport syndrome, autosomal recessive Alport syndrome (ClinVar).

How common is COL4A3 p.Pro1197= (c.3591A>G) in the general population?

COL4A3 p.Pro1197= (c.3591A>G) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Pro1197=

c.3591A>G · rs753945261 · VCV1195954

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

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 -2.4	GERP -4.1
Overall
CADD	0.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,978 alleles

Overall 6.21e-05% 1/1,609,048 alleles · ultra-rare exomes 1/1,456,760 · genomes 0/152,288 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL4A3
Protein: p.Pro1197=
Coding: c.3591A>G
MANE Select: NM_000091
dbSNP: rs753945261
Type: single nucleotide variant
Location: chr2:227297699 (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: autosomal recessive Alport syndrome

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-pro1197 (accessed [today's date]).

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