Is COL4A5 p.Gln835= (c.2505A>G) pathogenic?

COL4A5 p.Gln835= (c.2505A>G) is classified Conflicting classifications of pathogenicity in COL4A5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-05). Very rare (popmax 0.00175%, afr); Associated with X-linked Alport syndrome.

What condition is associated with COL4A5 p.Gln835= (c.2505A>G)?

COL4A5 p.Gln835= (c.2505A>G) is associated with X-linked Alport syndrome (ClinVar).

How common is COL4A5 p.Gln835= (c.2505A>G) in the general population?

COL4A5 p.Gln835= (c.2505A>G) is very rare (popmax 0.00175%, afr) (gnomAD).

How is Alport syndrome inherited?

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

COL4A5 p.Gln835=

c.2505A>G · rs1383769505 · VCV1116669

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Conditions

X-linked Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.46	donor gain · deltas
Constraint at this position
Conservation	phyloP 2	GERP -0.96, phastCons 1
Overall
CADD	15.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/57,001 alleles

Overall 9.47e-05% 1/1,055,462 alleles · very rare

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.Gln835=
Coding: c.2505A>G
MANE Select: NM_033380
dbSNP: rs1383769505
Type: single nucleotide variant
Location: chrX:108615020 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 835: 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.Gln835Ter Likely pathogenic ★ 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-gln835 (accessed [today's date]).

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