Is COL4A2 p.Pro1014= (c.3042A>C) pathogenic?

COL4A2 p.Pro1014= (c.3042A>C) is classified Benign/Likely benign in COL4A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-13). Very rare (popmax 0.00596%, nfe); Associated with brain small vessel disease 2A, autosomal dominant.

What condition is associated with COL4A2 p.Pro1014= (c.3042A>C)?

COL4A2 p.Pro1014= (c.3042A>C) is associated with brain small vessel disease 2A, autosomal dominant (ClinVar).

How common is COL4A2 p.Pro1014= (c.3042A>C) in the general population?

COL4A2 p.Pro1014= (c.3042A>C) is very rare (popmax 0.00596%, nfe) (gnomAD).

COL4A2 p.Pro1014=

c.3042A>C · rs200384476 · VCV882815

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00596%, nfe)

Conditions

brain small vessel disease 2A, autosomal dominant

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 -10	GERP -3.4
Overall
CADD	0.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00596% European (non-Finnish) · 70/1,174,934 alleles

Filtering AF 0.0048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0044%

Overall 0.0578% 926/1,601,938 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.3%	77
Remaining individualsnot grpmax-eligible	0.0484%	2,065
European (non-Finnish)grpmax	0.00596%	16,785

Finnish 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: COL4A2
Protein: p.Pro1014=
Coding: c.3042A>C
MANE Select: NM_001846
dbSNP: rs200384476
Type: single nucleotide variant
Location: chr13:110485671 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 1014: the 'triple-helical region' region

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

Similar variants

COL4A2 c.361-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A2 p.Gly619Asp Likely pathogenic ★★ same condition
COL4A2 c.2425+3G>A Uncertain significance ★★ same condition
COL4A2 p.Ala370Pro Uncertain significance ★★ ⚠ same condition
COL4A2 p.Ala95Asp Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1069Gln Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1069Trp Uncertain significance ★★ ⚠ same condition
COL4A2 p.Arg1617Gln Uncertain significance ★★ ⚠ 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/col4a2-p-pro1014 (accessed [today's date]).

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