Is COL4A2 p.Pro198= (c.594C>T) pathogenic?

COL4A2 p.Pro198= (c.594C>T) is classified Benign/Likely benign in COL4A2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 9.73%, afr) — too common for a highly-penetrant pathogenic allele; Associated with brain small vessel disease 2A, autosomal dominant.

What condition is associated with COL4A2 p.Pro198= (c.594C>T)?

COL4A2 p.Pro198= (c.594C>T) is associated with brain small vessel disease 2A, autosomal dominant, hemorrhage, intracerebral, susceptibility to (ClinVar).

COL4A2 p.Pro198=

Q: How common is COL4A2 p.Pro198= (c.594C>T) in the general population?

COL4A2 p.Pro198= (c.594C>T) is common (popmax 9.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.594C>T · rs74124319 · VCV311108

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 9.73%, afr) — too common for a highly-penetrant pathogenic allele

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 -15	GERP -3.1
Overall
CADD	2.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.73% African / African-American · 7,298/75,026 alleles

Filtering AF 9.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.46%

Overall 0.524% 8,451/1,614,182 alleles · common exomes 4,248/1,461,884 · genomes 4,203/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.73%	10
Remaining individualsnot grpmax-eligible	0.717%	140
Middle Eastern	0.643%	155
Admixed American	0.588%	170
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
East Asian	0.0334%	2,992
South Asian	0.0209%	4,794
European (non-Finnish)	0.0204%	4,896
Finnishnot grpmax-eligible	0.00937%	10,673

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.Pro198=
Coding: c.594C>T
MANE Select: NM_001846
dbSNP: rs74124319
Type: single nucleotide variant
Location: chr13:110430553 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 198: the 'disordered' region; 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

Also linked: hemorrhage, intracerebral, susceptibility to

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-pro198 (accessed [today's date]).

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