Is COL4A3 p.Pro299= (c.897C>T) pathogenic?

COL4A3 p.Pro299= (c.897C>T) is classified Likely benign in COL4A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with COL4A3 p.Pro299= (c.897C>T)?

COL4A3 p.Pro299= (c.897C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A3 p.Pro299= (c.897C>T) in the general population?

COL4A3 p.Pro299= (c.897C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

COL4A3 p.Pro299=

c.897C>T · rs368027756 · VCV1099777

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Inborn genetic diseases

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 -0.6	GERP -2.4, phastCons 0.061
Overall
CADD	10.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,854 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00136% 22/1,613,608 alleles · ultra-rare exomes 19/1,461,592 · genomes 3/152,016 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,476
South Asian	0.00439%	22,765
African / African-American	0.00401%	24,953
Finnishnot grpmax-eligible	0.00156%	63,990
European (non-Finnish)	0.000678%	147,477

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: COL4A3
Protein: p.Pro299=
Coding: c.897C>T
MANE Select: NM_000091
dbSNP: rs368027756
Type: single nucleotide variant
Location: chr2:227256034 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 48.64 · 2 PDB
Residue 299: the 'triple-helical region' region; the 'disordered' region

Full COL4A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL4A3 p.Arg1040Thr Uncertain significance ★★ ⚠ same condition
COL4A3 p.Arg1345His Uncertain significance ★★ ⚠ same condition
COL4A3 p.Arg1432Cys Uncertain significance ★★ ⚠ same condition
COL4A3 p.Arg1432Ser Uncertain significance ★★ ⚠ same condition
COL4A3 p.Arg4Gln Uncertain significance ★★ ⚠ same condition
COL4A3 p.Asp466Asn Uncertain significance ★★ ⚠ same condition
COL4A3 p.Glu956Asp Uncertain significance ★★ ⚠ same condition
COL4A3 p.Gly1110Arg 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/col4a3-p-pro299 (accessed [today's date]).

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