Is COL4A3 p.Pro1203= (c.3609G>A) pathogenic?

COL4A3 p.Pro1203= (c.3609G>A) is classified Conflicting classifications of pathogenicity in COL4A3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0499%, mid); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro1203= (c.3609G>A)?

COL4A3 p.Pro1203= (c.3609G>A) is associated with autosomal dominant Alport syndrome, Alport syndrome 3b, autosomal recessive, hematuria, benign familial, 2 (ClinVar).

How common is COL4A3 p.Pro1203= (c.3609G>A) in the general population?

COL4A3 p.Pro1203= (c.3609G>A) is ultra-rare (popmax 0.0499%, 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.Pro1203=

c.3609G>A · rs1045022382 · VCV2164833

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 0.0499%, mid)

Conditions

autosomal dominant 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 -12	GERP -4.1
Overall
CADD	0.172	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0499% Middle Eastern · 3/6,008 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00724%

Overall 0.00165% 24/1,455,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0499%	2,003
East Asian	0.00447%	22,386
Remaining individualsnot grpmax-eligible	0.00321%	31,128
South Asian	0.00224%	44,581
European (non-Finnish)	0.00127%	78,529

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.Pro1203=
Coding: c.3609G>A
MANE Select: NM_000091
dbSNP: rs1045022382
Type: single nucleotide variant
Location: chr2:227297717 (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 1203: the 'triple-helical region' region; the 'disordered' region

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

Similar variants

COL4A3 p.Pro1203Leu Uncertain significance ★ ⚠ same residue
COL4A3 p.Pro1203Ser Uncertain significance ★ ⚠ same residue
COL4A3 c.1114+1G>A Likely pathogenic ★★ same condition
COL4A3 c.1114+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.2656+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.2746+1G>T Pathogenic ★★ same condition
COL4A3 c.2747-1G>C 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-pro1203 (accessed [today's date]).

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