Is COL4A3 p.Pro879= (c.2637G>A) pathogenic?

COL4A3 p.Pro879= (c.2637G>A) is classified Likely benign in COL4A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.012%, afr); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro879= (c.2637G>A)?

COL4A3 p.Pro879= (c.2637G>A) is associated with autosomal dominant Alport syndrome, autosomal recessive Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A3 p.Pro879= (c.2637G>A) in the general population?

COL4A3 p.Pro879= (c.2637G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Pro879=

c.2637G>A · rs755312698 · VCV1077660

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

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 0.83	GERP -1.1, phastCons 0.62
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,772 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00205% 33/1,613,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,308
South Asian	0.00329%	30,352
East Asian	0.00223%	44,844
Admixed American	0.00167%	59,958
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.00153%	65,543

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.Pro879=
Coding: c.2637G>A
MANE Select: NM_000091
dbSNP: rs755312698
Type: single nucleotide variant
Location: chr2:227282513 (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 879: 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 p.Pro879Leu Uncertain significance ★★ ⚠ same residue
COL4A3 p.Pro879Gln 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.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

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-pro879 (accessed [today's date]).

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