Is COL4A2 p.Asp244= (c.732C>T) pathogenic?

COL4A2 p.Asp244= (c.732C>T) is classified Benign/Likely benign in COL4A2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.82%, afr); Associated with brain small vessel disease 2A, autosomal dominant.

What condition is associated with COL4A2 p.Asp244= (c.732C>T)?

COL4A2 p.Asp244= (c.732C>T) is associated with brain small vessel disease 2A, autosomal dominant, hemorrhage, intracerebral, susceptibility to (ClinVar).

How common is COL4A2 p.Asp244= (c.732C>T) in the general population?

COL4A2 p.Asp244= (c.732C>T) is low-frequency (popmax 2.82%, afr) (gnomAD).

COL4A2 p.Asp244=

c.732C>T · rs144319016 · VCV311110

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.82%, 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>G here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.6	GERP -2
Overall
CADD	5.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.82% African / African-American · 2,114/74,894 alleles

Filtering AF 2.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.68%

Overall 0.15% 2,428/1,613,886 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.82%	35
Admixed American	0.182%	550
Remaining individualsnot grpmax-eligible	0.163%	613
Middle Eastern	0.132%	758
European (non-Finnish)	0.00771%	12,967
South Asian	0.00329%	30,352
East Asian	0.00223%	44,884

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.Asp244=
Coding: c.732C>T
MANE Select: NM_001846
dbSNP: rs144319016
Type: single nucleotide variant
Location: chr13:110436274 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 244: 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-asp244 (accessed [today's date]).

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