Is COL4A4 p.Lys290= (c.870G>A) pathogenic?

COL4A4 p.Lys290= (c.870G>A) is classified Pathogenic in COL4A4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-24). Very rare (popmax 0.00112%, sas); Associated with Alport syndrome.

What condition is associated with COL4A4 p.Lys290= (c.870G>A)?

COL4A4 p.Lys290= (c.870G>A) is associated with Alport syndrome (ClinVar).

How common is COL4A4 p.Lys290= (c.870G>A) in the general population?

COL4A4 p.Lys290= (c.870G>A) is very rare (popmax 0.00112%, sas) (gnomAD).

How is Alport syndrome inherited?

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

COL4A4 p.Lys290=

c.870G>A · rs2060620860 · VCV1036012

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Conditions

Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.89	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.76	loss · gain 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,334 alleles

Overall 6.86e-05% 1/1,457,544 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: COL4A4
Protein: p.Lys290=
Coding: c.870G>A
MANE Select: NM_000092
dbSNP: rs2060620860
Type: single nucleotide variant
Location: chr2:227103144 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 290: the 'triple-helical region' region

Full COL4A4 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

For Alport syndrome (Orphanet):

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

Similar variants

COL4A4 p.Lys290Ter Pathogenic ★ same residue
COL4A4 c.1030-2A>C Likely pathogenic ★★ same condition
COL4A4 c.1369+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A4 c.1370-2A>C Likely pathogenic ★★ same condition
COL4A4 c.1696+1G>A Likely pathogenic ★★ same condition
COL4A4 c.1696+1G>T Likely pathogenic ★★ same condition
COL4A4 c.1697-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A4 c.1803+2T>C 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/col4a4-p-lys290 (accessed [today's date]).

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