Is COL4A6 p.Leu535= (c.1603C>T) pathogenic?

COL4A6 p.Leu535= (c.1603C>T) is classified Likely benign in COL4A6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-22). Absent from gnomAD v4.1; Associated with COL4A6-related disorder.

What condition is associated with COL4A6 p.Leu535= (c.1603C>T)?

COL4A6 p.Leu535= (c.1603C>T) is associated with COL4A6-related disorder (ClinVar).

How common is COL4A6 p.Leu535= (c.1603C>T) in the general population?

COL4A6 p.Leu535= (c.1603C>T) is absent from gnomAD v4.1 (gnomAD).

COL4A6 p.Leu535=

c.1603C>T · rs2522048566 · VCV3037373

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

COL4A6-related disorder

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 4.7	GERP -0.28, phastCons 1
Overall
CADD	1.179	PHRED · no single calibrated threshold — expert panels disagree

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: COL4A6
Protein: p.Leu535=
Coding: c.1603C>T
MANE Select: NM_033641
dbSNP: rs2522048566
Type: single nucleotide variant
Location: chrX:108188012 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 535: the 'triple-helical region' region; the 'disordered' region

Full COL4A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL4A6-related disorder

Similar variants

COL4A6 p.Glu453Asp Uncertain significance ★★ ⚠ same condition
COL4A6 p.Val1555Ile Uncertain significance ★★ ⚠ same condition
COL4A6 p.Ala1548Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
COL4A6 p.Ile1152Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
COL4A6 p.Pro383Ser Uncertain significance ★ ⚠ same condition
COL4A6 p.Ser1420Thr Uncertain significance ★ ⚠ same condition
COL4A6 p.Arg517Gln Uncertain significance ⚠ same condition
COL4A6 p.Ile356Val Uncertain significance ⚠ 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/col4a6-p-leu535 (accessed [today's date]).

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