Is COL4A3 p.Pro905= (c.2715C>T) pathogenic?

COL4A3 p.Pro905= (c.2715C>T) is classified Benign/Likely benign in COL4A3 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-02). Common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Alport syndrome.

What condition is associated with COL4A3 p.Pro905= (c.2715C>T)?

COL4A3 p.Pro905= (c.2715C>T) is associated with Alport syndrome, atypical hemolytic-uremic syndrome (ClinVar).

How is Alport syndrome inherited?

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

COL4A3 p.Pro905=

Q: How common is COL4A3 p.Pro905= (c.2715C>T) in the general population?

COL4A3 p.Pro905= (c.2715C>T) is common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2715C>T · rs75519005 · VCV254988

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele

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 0.71	GERP -5.1, phastCons 0.47
Overall
CADD	2.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.56% African / African-American · 4,920/75,000 alleles

Filtering AF 6.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.34%

Overall 0.338% 5,453/1,614,046 alleles · common exomes 2,670/1,461,744 · genomes 2,783/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.56%	15
Remaining individualsnot grpmax-eligible	0.438%	228
Admixed American	0.316%	316
Middle Eastern	0.148%	674
South Asian	0.0165%	6,072
European (non-Finnish)	0.00381%	26,221

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.Pro905=
Coding: c.2715C>T
MANE Select: NM_000091
dbSNP: rs75519005
Type: single nucleotide variant
Location: chr2:227283825 (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 905: 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

Also linked: atypical hemolytic-uremic syndrome

For Alport syndrome (Orphanet):

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

Similar variants

COL4A3 p.Pro905Leu Uncertain significance ★★ ⚠ same residue
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

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-pro905 (accessed [today's date]).

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