Is COL4A3 p.Pro135= (c.405A>G) pathogenic?

COL4A3 p.Pro135= (c.405A>G) is classified Likely benign in COL4A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-20). Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with COL4A3 p.Pro135= (c.405A>G)?

COL4A3 p.Pro135= (c.405A>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL4A3 p.Pro135= (c.405A>G) in the general population?

COL4A3 p.Pro135= (c.405A>G) is very rare (popmax 0.004%, afr) (gnomAD).

COL4A3 p.Pro135=

c.405A>G · rs1574675832 · VCV666678

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 -0.39	GERP -4.9
Overall
CADD	7.097	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,002 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000274% 4/1,460,350 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,001
Remaining individualsnot grpmax-eligible	0.0016%	62,448

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.Pro135=
Coding: c.405A>G
MANE Select: NM_000091
dbSNP: rs1574675832
Type: single nucleotide variant
Location: chr2:227246702 (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 135: the 'triple-helical region' 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-pro135 (accessed [today's date]).

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