Is COL4A3 p.Asp466= (c.1398T>C) pathogenic?

COL4A3 p.Asp466= (c.1398T>C) is classified Benign/Likely benign in COL4A3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.91%, afr); Associated with Alport syndrome.

What condition is associated with COL4A3 p.Asp466= (c.1398T>C)?

COL4A3 p.Asp466= (c.1398T>C) is associated with Alport syndrome (ClinVar).

How common is COL4A3 p.Asp466= (c.1398T>C) in the general population?

COL4A3 p.Asp466= (c.1398T>C) is low-frequency (popmax 1.91%, afr) (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Asp466=

c.1398T>C · rs145833114 · VCV254980

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, afr)

Conditions

Alport syndrome

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 -1.4	GERP -5.2
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.91% African / African-American · 1,435/74,990 alleles

Filtering AF 1.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.8%

Overall 0.0977% 1,576/1,613,546 alleles · low-frequency exomes 758/1,461,258 · genomes 818/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.91%	52
Remaining individualsnot grpmax-eligible	0.128%	781
Middle Eastern	0.066%	1,516
Admixed American	0.0633%	1,579
South Asian	0.0033%	30,345
European (non-Finnish)	0.00136%	73,724

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: COL4A3
Protein: p.Asp466=
Coding: c.1398T>C
MANE Select: NM_000091
dbSNP: rs145833114
Type: single nucleotide variant
Location: chr2:227266499 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 48.64 · 2 PDB
Residue 466: the 'triple-helical region' region; the 'disordered' region

Full COL4A3 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

COL4A3 p.Asp466Asn Uncertain significance ★★ ⚠ same residue
COL4A3 c.1114+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1504+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1927+1G>A Likely pathogenic ★★ same condition
COL4A3 c.2020+1G>T Likely pathogenic ★★ same condition
COL4A3 c.2224-2A>G 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/col4a3-p-asp466 (accessed [today's date]).

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