Is COL4A2 p.Pro1572= (c.4716G>A) pathogenic?

COL4A2 p.Pro1572= (c.4716G>A) is classified Benign/Likely benign in COL4A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-22). Ultra-rare (popmax 0.0536%, nfe); Associated with brain small vessel disease 2A, autosomal dominant.

What condition is associated with COL4A2 p.Pro1572= (c.4716G>A)?

COL4A2 p.Pro1572= (c.4716G>A) is associated with brain small vessel disease 2A, autosomal dominant (ClinVar).

How common is COL4A2 p.Pro1572= (c.4716G>A) in the general population?

COL4A2 p.Pro1572= (c.4716G>A) is ultra-rare (popmax 0.0536%, nfe) (gnomAD).

COL4A2 p.Pro1572=

c.4716G>A · rs201510187 · VCV754762

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0536%, nfe)

Conditions

brain small vessel disease 2A, autosomal dominant

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.2	GERP -3.8
Overall
CADD	2.891	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0536% European (non-Finnish) · 632/1,180,046 alleles

Filtering AF 0.0501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0487%

Overall 0.0411% 664/1,614,108 alleles · ultra-rare exomes 620/1,461,876 · genomes 44/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0536%	1,867
Remaining individualsnot grpmax-eligible	0.0272%	3,676
African / African-American	0.0173%	5,765
Admixed American	0.00167%	60,004
Finnishnot grpmax-eligible	0.00156%	64,036

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: COL4A2
Protein: p.Pro1572=
Coding: c.4716G>A
MANE Select: NM_001846
dbSNP: rs201510187
Type: single nucleotide variant
Location: chr13:110508056 (GRCh38)

Full COL4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

brain small vessel disease 2A, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/col4a2-p-pro1572 (accessed [today's date]).

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