Is COL4A3 p.Pro620= (c.1860C>T) pathogenic?

COL4A3 p.Pro620= (c.1860C>T) is classified Likely benign in COL4A3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00891%, eas); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro620= (c.1860C>T)?

COL4A3 p.Pro620= (c.1860C>T) is associated with autosomal dominant Alport syndrome, autosomal recessive Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A3 p.Pro620= (c.1860C>T) in the general population?

COL4A3 p.Pro620= (c.1860C>T) is very rare (popmax 0.00891%, 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.Pro620=

c.1860C>T · rs376896231 · VCV1120404

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

autosomal dominant 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 -2.8	GERP -3.7
Overall
CADD	0.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,872 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000991% 16/1,613,958 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,680
East Asiangrpmax	0.00891%	11,218
Admixed American	0.00167%	59,996

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro620=
Coding: c.1860C>T
MANE Select: NM_000091
dbSNP: rs376896231
Type: single nucleotide variant
Location: chr2:227273050 (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 620: the 'triple-helical region' region; the 'disordered' region

Full COL4A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: autosomal recessive Alport syndrome hematuria, benign familial

For Alport syndrome (Orphanet):

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

Similar variants

COL4A3 p.Pro620His Uncertain significance ★ ⚠ same residue
COL4A3 c.1114+1G>A Likely pathogenic ★★ same condition
COL4A3 c.1114+2T>C 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.2489-1G>A Likely pathogenic ★★ same condition
COL4A3 c.2656+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.2746+1G>T 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-pro620 (accessed [today's date]).

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