Is COL4A5 p.Pro783= (c.2349G>A) pathogenic?

COL4A5 p.Pro783= (c.2349G>A) is classified Benign in COL4A5 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 33.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with X-linked Alport syndrome.

What condition is associated with COL4A5 p.Pro783= (c.2349G>A)?

COL4A5 p.Pro783= (c.2349G>A) is associated with X-linked Alport syndrome (ClinVar).

How is Alport syndrome inherited?

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

COL4A5 p.Pro783=

Q: How common is COL4A5 p.Pro783= (c.2349G>A) in the general population?

COL4A5 p.Pro783= (c.2349G>A) is common (popmax 33.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2349G>A · rs3747408 · VCV24511

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 33.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

X-linked 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 0.67	GERP 0.49, phastCons 0.93
Overall
CADD	7.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.8% African / African-American · 19,188/56,701 alleles

Filtering AF 33.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.3%

Overall 2.42% 29,226/1,208,260 alleles · common exomes 17,647/1,097,288 · genomes 11,579/110,972 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.8%	3
East Asian	12.6%	8
Admixed American	4.92%	20
Remaining individualsnot grpmax-eligible	4.13%	24
South Asian	1.53%	65
Middle Eastern	1.1%	91
Ashkenazi Jewishnot grpmax-eligible	0.354%	282
European (non-Finnish)	0.065%	1,539
Finnishnot grpmax-eligible	0.0172%	5,811

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: COL4A5
Protein: p.Pro783=
Coding: c.2349G>A
MANE Select: NM_033380
dbSNP: rs3747408
Type: single nucleotide variant
Location: chrX:108606846 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 783: the 'triple-helical region' region; the 'disordered' region

Full COL4A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked 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

COL4A5 p.Pro783Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
COL4A5 c.1033-1G>A Pathogenic ★★ same condition
COL4A5 c.1033-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.1339+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.141+1G>A Pathogenic ★★ same condition
COL4A5 c.1424-20T>A Pathogenic/Likely pathogenic ★★ same condition
COL4A5 c.1516+1G>C Pathogenic ★★ same condition
COL4A5 c.1780-1G>T 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/col4a5-p-pro783 (accessed [today's date]).

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