Is COL4A5 p.Arg1569Pro (c.4706G>C) pathogenic?

COL4A5 p.Arg1569Pro (c.4706G>C) is classified Likely pathogenic in COL4A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-28). AlphaMissense: likely pathogenic (0.9673); Absent from gnomAD v4.1; Associated with X-linked Alport syndrome.

What condition is associated with COL4A5 p.Arg1569Pro (c.4706G>C)?

COL4A5 p.Arg1569Pro (c.4706G>C) is associated with X-linked Alport syndrome (ClinVar).

How common is COL4A5 p.Arg1569Pro (c.4706G>C) in the general population?

COL4A5 p.Arg1569Pro (c.4706G>C) is absent from gnomAD v4.1 (gnomAD).

How is Alport syndrome inherited?

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

What do computational predictors say about COL4A5 p.Arg1569Pro (c.4706G>C)?

AlphaMissense predicts likely pathogenic (score 0.9673) — an in-silico prediction, not a clinical call.

COL4A5 p.Arg1569Pro

c.4706G>C · rs281874743 · VCV3235211

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9673 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Alport syndrome

Computational evidence

Protein change
AlphaMissense	0.9673	likely pathogenic ✓ concordant with ClinVar · top 7% in COL4A5
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.77	donor loss · deltas
Pangolin	Δ0.58	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1563P vs ClinVar R1569P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL4A5
Protein: p.Arg1569Pro
Coding: c.4706G>C
MANE Select: NM_033380
dbSNP: rs281874743
Type: single nucleotide variant
Location: chrX:108692925 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 1569: the collagen iv nc1 domain; a β-strand

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.Arg1569Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
COL4A5 p.Arg1569Ter Pathogenic ★★ same residue
COL4A5 p.Arg1569= Uncertain significance 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

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-arg1569pro (accessed [today's date]).

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