Is COL4A1 p.Asp230= (c.690C>T) pathogenic?

COL4A1 p.Asp230= (c.690C>T) is classified Benign/Likely benign in COL4A1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Rare (popmax 0.283%, sas); Associated with autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome.

What condition is associated with COL4A1 p.Asp230= (c.690C>T)?

COL4A1 p.Asp230= (c.690C>T) is associated with autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, brain small vessel disease 1 with or without ocular anomalies, retinal arterial tortuosity (ClinVar).

How common is COL4A1 p.Asp230= (c.690C>T) in the general population?

COL4A1 p.Asp230= (c.690C>T) is rare (popmax 0.283%, sas) (gnomAD).

How is HANAC syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

COL4A1 p.Asp230=

c.690C>T · rs149688210 · VCV311074

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.283%, sas)

Conditions

autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

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 · G>C here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.014	GERP -3.5, phastCons 0.4
Overall
CADD	6.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.283% South Asian · 258/91,082 alleles

Filtering AF 0.255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0691% 1,115/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.44%	69
South Asiangrpmax	0.283%	353
Remaining individualsnot grpmax-eligible	0.158%	631
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0274%	3,653
Admixed American	0.00666%	15,006
Finnishnot grpmax-eligible	0.00156%	64,026
African / African-American	0.00133%	75,050

Ashkenazi Jewish 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: COL4A1
Protein: p.Asp230=
Coding: c.690C>T
MANE Select: NM_001845
dbSNP: rs149688210
Type: single nucleotide variant
Location: chr13:110208852 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.43 · 4 PDB
Residue 230: the 'disordered' region; the 'triple-helical region' region

Full COL4A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brain small vessel disease 1 with or without ocular anomalies retinal arterial tortuosity microangiopathy and leukoencephalopathy, pontine, autosomal dominant hemorrhage, intracerebral, susceptibility to

For HANAC syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

COL4A1 c.1991-2A>G Likely pathogenic ★★ same condition
COL4A1 c.2458+1G>A Pathogenic ★★ same condition
COL4A1 c.2458+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A1 c.3742+1G>A Pathogenic ★★ same condition
COL4A1 c.388-1G>C Pathogenic/Likely pathogenic ★★ same condition
COL4A1 c.4250-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A1 c.*32G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A1 p.Arg1063Ter Pathogenic/Likely pathogenic ★★ 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/col4a1-p-asp230 (accessed [today's date]).

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