Is COL4A3 p.Pro513= (c.1539A>C) pathogenic?

COL4A3 p.Pro513= (c.1539A>C) is classified Likely benign in COL4A3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-23). Rare (popmax 0.132%, mid); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro513= (c.1539A>C)?

COL4A3 p.Pro513= (c.1539A>C) is associated with autosomal dominant Alport syndrome, autosomal recessive Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A3 p.Pro513= (c.1539A>C) in the general population?

COL4A3 p.Pro513= (c.1539A>C) is rare (popmax 0.132%, 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.Pro513=

c.1539A>C · rs749945759 · VCV795485

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, 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 -3.9	GERP -5.4
Overall
CADD	0.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.0026% 42/1,613,870 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00266%	37,528
South Asian	0.0022%	45,537
European (non-Finnish)	0.00203%	49,159

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.Pro513=
Coding: c.1539A>C
MANE Select: NM_000091
dbSNP: rs749945759
Type: single nucleotide variant
Location: chr2:227269944 (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 513: 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: autosomal recessive Alport syndrome hematuria, benign familial

For Alport syndrome (Orphanet):

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

Similar variants

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.1504+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.2489-1G>A 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-pro513 (accessed [today's date]).

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