Is COL4A4 p.Ser1102= (c.3306C>T) pathogenic?

COL4A4 p.Ser1102= (c.3306C>T) is classified Likely benign in COL4A4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.056%, afr); Associated with autosomal recessive Alport syndrome.

What condition is associated with COL4A4 p.Ser1102= (c.3306C>T)?

COL4A4 p.Ser1102= (c.3306C>T) is associated with autosomal recessive Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A4 p.Ser1102= (c.3306C>T) in the general population?

COL4A4 p.Ser1102= (c.3306C>T) is ultra-rare (popmax 0.056%, afr) (gnomAD).

How is Alport syndrome inherited?

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

COL4A4 p.Ser1102=

c.3306C>T · rs200065408 · VCV1096663

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, afr)

Conditions

autosomal recessive 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 -6.5	GERP -3.3
Overall
CADD	0.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% African / African-American · 42/75,042 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00997% 161/1,614,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.056%	1,787
Admixed American	0.0317%	3,159
South Asian	0.0143%	7,005
Remaining individualsnot grpmax-eligible	0.0112%	8,930
East Asian	0.0111%	8,974
European (non-Finnish)	0.00636%	15,732

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.Ser1102=
Coding: c.3306C>T
MANE Select: NM_000092
dbSNP: rs200065408
Type: single nucleotide variant
Location: chr2:227043168 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.03 · 2 PDB
Residue 1102: the 'triple-helical region' region; the 'disordered' region

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

Disease context

autosomal recessive Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hematuria, benign familial

For Alport syndrome (Orphanet):

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

Similar variants

COL4A4 p.Ser1102Phe Uncertain significance ★★ ⚠ same residue
COL4A4 p.Ser1102Thr 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.1459+1G>A Pathogenic ★★ same condition
COL4A4 c.1696+1G>A Likely pathogenic ★★ same condition
COL4A4 c.1696+1G>T 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-ser1102 (accessed [today's date]).

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