Is COL4A3 p.Pro1090= (c.3270A>C) pathogenic?

COL4A3 p.Pro1090= (c.3270A>C) is classified Conflicting classifications of pathogenicity in COL4A3 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-24). Rare (popmax 0.105%, amr); Associated with Alport syndrome.

What condition is associated with COL4A3 p.Pro1090= (c.3270A>C)?

COL4A3 p.Pro1090= (c.3270A>C) is associated with Alport syndrome (ClinVar).

How common is COL4A3 p.Pro1090= (c.3270A>C) in the general population?

COL4A3 p.Pro1090= (c.3270A>C) is rare (popmax 0.105%, amr) (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Pro1090=

c.3270A>C · rs201989155 · VCV254992

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, amr)

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 -0.44	GERP -4.4
Overall
CADD	3.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Admixed American · 63/60,026 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0766%

Overall 0.0232% 374/1,613,924 alleles · rare exomes 329/1,461,602 · genomes 45/152,322 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	953
Remaining individualsnot grpmax-eligible	0.0352%	2,840
European (non-Finnish)	0.0239%	4,185
African / African-American	0.00799%	12,508
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Pro1090=
Coding: c.3270A>C
MANE Select: NM_000091
dbSNP: rs201989155
Type: single nucleotide variant
Location: chr2:227293250 (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 1090: 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 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
COL4A3 c.2020+1G>T Likely pathogenic ★★ same condition
COL4A3 c.2224-2A>G Likely pathogenic ★★ same condition
COL4A3 c.2375-2A>G 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-pro1090 (accessed [today's date]).

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