Is COL4A4 p.Ala401= (c.1203A>G) pathogenic?

COL4A4 p.Ala401= (c.1203A>G) is classified Conflicting classifications of pathogenicity in COL4A4 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-07-22). Very rare (popmax 0.000424%, nfe); Associated with hematuria, benign familial, 1.

What condition is associated with COL4A4 p.Ala401= (c.1203A>G)?

COL4A4 p.Ala401= (c.1203A>G) is associated with hematuria, benign familial, 1, autosomal recessive Alport syndrome, Alport syndrome (ClinVar).

How common is COL4A4 p.Ala401= (c.1203A>G) in the general population?

COL4A4 p.Ala401= (c.1203A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

COL4A4 p.Ala401=

c.1203A>G · rs778832152 · VCV422613

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

hematuria, benign familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.61	donor gain · deltas
Pangolin	Δ0.60	gain · loss 0.55 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.1	GERP 1.8, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,526 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,432 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.Ala401=
Coding: c.1203A>G
MANE Select: NM_000092
dbSNP: rs778832152
Type: single nucleotide variant
Location: chr2:227098695 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 401: the 'triple-helical region' region

Full COL4A4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hematuria, benign familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive Alport syndrome Alport syndrome

Similar variants

COL4A4 p.Ala401Val Benign/Likely benign ★★ same residue
COL4A4 p.Ala401Pro Uncertain significance ★ ⚠ same residue
COL4A4 c.1030-2A>C Likely pathogenic ★★ same condition
COL4A4 c.1099+1G>T Pathogenic/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.1459+1G>A Pathogenic ★★ same condition
COL4A4 c.1696+1G>A 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-ala401 (accessed [today's date]).

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