Is COL4A3 p.Pro238= (c.714G>A) pathogenic?

COL4A3 p.Pro238= (c.714G>A) is classified Likely benign in COL4A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-13). Very rare (popmax 0.00549%, sas); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro238= (c.714G>A)?

COL4A3 p.Pro238= (c.714G>A) is associated with autosomal dominant Alport syndrome, autosomal recessive Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A3 p.Pro238= (c.714G>A) in the general population?

COL4A3 p.Pro238= (c.714G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

How is Alport syndrome inherited?

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

COL4A3 p.Pro238=

c.714G>A · rs555225084 · VCV750930

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

autosomal dominant Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.5	GERP -5.2
Overall
CADD	0.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,066 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00335% 54/1,613,970 alleles · very rare exomes 50/1,461,766 · genomes 4/152,204 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,213
Admixed American	0.005%	20,003
African / African-American	0.004%	24,999
European (non-Finnish)	0.00339%	29,498
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Pro238=
Coding: c.714G>A
MANE Select: NM_000091
dbSNP: rs555225084
Type: single nucleotide variant
Location: chr2:227253587 (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 238: the 'triple-helical region' region; the 'disordered' region

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

Disease context

autosomal dominant Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive Alport syndrome hematuria, benign familial

For Alport syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

COL4A3 p.Pro238fs Pathogenic ★★ same residue
COL4A3 p.Pro238Arg Uncertain significance ★ ⚠ same residue
COL4A3 p.Pro238Ser Uncertain significance ★ ⚠ same residue
COL4A3 p.Pro238Leu Likely benign ★ ⚠ same residue
COL4A3 c.1114+1G>A Likely pathogenic ★★ same condition
COL4A3 c.1114+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1504+1G>A 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/col4a3-p-pro238 (accessed [today's date]).

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