Is COL4A5 p.Pro1263Gln (c.3788C>A) pathogenic?

COL4A5 p.Pro1263Gln (c.3788C>A) is classified Uncertain significance in COL4A5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0796); Very rare (popmax 0.000571%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL4A5 p.Pro1263Gln (c.3788C>A)?

COL4A5 p.Pro1263Gln (c.3788C>A) is associated with Inborn genetic diseases, X-linked Alport syndrome (ClinVar).

How common is COL4A5 p.Pro1263Gln (c.3788C>A) in the general population?

COL4A5 p.Pro1263Gln (c.3788C>A) is very rare (popmax 0.000571%, nfe) (gnomAD).

What do computational predictors say about COL4A5 p.Pro1263Gln (c.3788C>A)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

COL4A5 p.Pro1263Gln

c.3788C>A · VCV3597967

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000571%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.667	pathogenic-leaning
SaProt	LLR -10.07	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 256 kb · p 6e-09 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000571% European (non-Finnish) · 5/875,707 alleles

Filtering AF 0.000167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000473% 5/1,056,442 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.Pro1263Gln
Coding: c.3788C>A
MANE Select: NM_033380
Type: single nucleotide variant
Location: chrX:108668502 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 1263: the 'triple-helical region' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked Alport syndrome

Similar variants

COL4A5 p.Pro1263Ser 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
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-pro1263gln (accessed [today's date]).

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