Is COL4A2 p.Ile261= (c.783C>A) pathogenic?

COL4A2 p.Ile261= (c.783C>A) is classified Likely benign in COL4A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). Very rare (popmax 0.00763%, nfe); Associated with brain small vessel disease 2A, autosomal dominant.

What condition is associated with COL4A2 p.Ile261= (c.783C>A)?

COL4A2 p.Ile261= (c.783C>A) is associated with brain small vessel disease 2A, autosomal dominant (ClinVar).

How common is COL4A2 p.Ile261= (c.783C>A) in the general population?

COL4A2 p.Ile261= (c.783C>A) is very rare (popmax 0.00763%, nfe) (gnomAD).

COL4A2 p.Ile261=

c.783C>A · rs369814411 · VCV311111

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00763%, 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 -4.9	GERP -0.91
Overall
CADD	0.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00763% European (non-Finnish) · 90/1,180,036 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.0057% 92/1,613,956 alleles · very rare exomes 77/1,461,886 · genomes 15/152,070 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,112
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ile261=
Coding: c.783C>A
MANE Select: NM_001846
dbSNP: rs369814411
Type: single nucleotide variant
Location: chr13:110436325 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.97 · 4 PDB
Residue 261: 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-ile261 (accessed [today's date]).

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