Is COL4A3 p.Pro105= (c.315T>C) pathogenic?

COL4A3 p.Pro105= (c.315T>C) is classified Likely benign in COL4A3 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-03-18). Very rare (popmax 0.00446%, eas); Associated with Alport syndrome.

What condition is associated with COL4A3 p.Pro105= (c.315T>C)?

COL4A3 p.Pro105= (c.315T>C) is associated with Alport syndrome (ClinVar).

How common is COL4A3 p.Pro105= (c.315T>C) in the general population?

COL4A3 p.Pro105= (c.315T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Pro105=

c.315T>C · rs371460434 · VCV794933

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -3.3	GERP -5.1
Overall
CADD	6.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,818 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.00031% 5/1,613,056 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,409
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.00017%	589,696

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.Pro105=
Coding: c.315T>C
MANE Select: NM_000091
dbSNP: rs371460434
Type: single nucleotide variant
Location: chr2:227244986 (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 105: the 'triple-helical region' 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 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
COL4A3 c.2375-2A>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-pro105 (accessed [today's date]).

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