Is COL4A2 p.Val192= (c.576C>T) pathogenic?

COL4A2 p.Val192= (c.576C>T) is classified Benign/Likely benign in COL4A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-20). Rare (popmax 0.576%, afr); Associated with brain small vessel disease 2A, autosomal dominant.

What condition is associated with COL4A2 p.Val192= (c.576C>T)?

COL4A2 p.Val192= (c.576C>T) is associated with brain small vessel disease 2A, autosomal dominant (ClinVar).

How common is COL4A2 p.Val192= (c.576C>T) in the general population?

COL4A2 p.Val192= (c.576C>T) is rare (popmax 0.576%, afr) (gnomAD).

COL4A2 p.Val192=

c.576C>T · rs190117538 · VCV311107

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.576%, afr)

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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.6	GERP -3.1
Overall
CADD	2.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.576% African / African-American · 432/75,010 alleles

Filtering AF 0.531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.513%

Overall 0.0321% 518/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.576%	174
Admixed American	0.0517%	1,936
Remaining individualsnot grpmax-eligible	0.04%	2,500
Middle Eastern	0.0165%	6,058
Finnishnot grpmax-eligible	0.0125%	8,003
South Asian	0.00549%	18,208
European (non-Finnish)	0.00136%	73,752

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.Val192=
Coding: c.576C>T
MANE Select: NM_001846
dbSNP: rs190117538
Type: single nucleotide variant
Location: chr13:110430427 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 192: a UniProt-annotated variant site (does not affect col4a2 and col4a1 secretion); 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

Similar variants

COL4A2 p.Val192Phe Benign/Likely benign ★★ same residue
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

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-val192 (accessed [today's date]).

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