Is COL4A5 p.Asp1431= (c.4293C>T) pathogenic?

COL4A5 p.Asp1431= (c.4293C>T) is classified Benign in COL4A5 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 31.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with X-linked Alport syndrome.

What condition is associated with COL4A5 p.Asp1431= (c.4293C>T)?

COL4A5 p.Asp1431= (c.4293C>T) is associated with X-linked Alport syndrome (ClinVar).

How is Alport syndrome inherited?

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

COL4A5 p.Asp1431=

Q: How common is COL4A5 p.Asp1431= (c.4293C>T) in the general population?

COL4A5 p.Asp1431= (c.4293C>T) is common (popmax 31.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4293C>T · rs61746140 · VCV24722

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 31.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

X-linked Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.142	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.097	GERP -1.8, phastCons 0.93
Overall
CADD	5.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.8% African / African-American · 17,994/56,594 alleles

Filtering AF 31.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.2%

Overall 2.11% 25,470/1,207,264 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.8%	3
East Asian	8.02%	12
Admixed American	4.62%	22
Remaining individualsnot grpmax-eligible	3.18%	31
Middle Eastern	1.01%	99
South Asian	0.964%	104
Ashkenazi Jewishnot grpmax-eligible	0.355%	282
European (non-Finnish)	0.0545%	1,836
Finnishnot grpmax-eligible	0.0129%	7,743

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.Asp1431=
Coding: c.4293C>T
MANE Select: NM_033380
dbSNP: rs61746140
Type: single nucleotide variant
Location: chrX:108686107 (GRCh38)
Structure: AlphaFold pLDDT 49.04 · 2 PDB
Residue 1431: the 'triple-helical region' region; the 'disordered' region

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 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
COL4A5 c.2042-2A>G 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-asp1431 (accessed [today's date]).

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