Is COL4A3 p.Pro25Ser (c.73C>T) pathogenic?

COL4A3 p.Pro25Ser (c.73C>T) is classified Benign/Likely benign in COL4A3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0856); Low-frequency (popmax 3.13%, afr); Associated with kidney disorder.

What condition is associated with COL4A3 p.Pro25Ser (c.73C>T)?

COL4A3 p.Pro25Ser (c.73C>T) is associated with kidney disorder, Alport syndrome (ClinVar).

How common is COL4A3 p.Pro25Ser (c.73C>T) in the general population?

COL4A3 p.Pro25Ser (c.73C>T) is low-frequency (popmax 3.13%, afr) (gnomAD).

What do computational predictors say about COL4A3 p.Pro25Ser (c.73C>T)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

COL4A3 p.Pro25Ser

c.73C>T · rs139271412 · VCV255004

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.13%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

kidney disorder

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.29, phastCons 0.89
Regional constraint	o/e 1.09	unconstrained · MANE · 89 kb · p 0.088 · regional, not allelic
Overall
CADD	8.707	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.13% African / African-American · 2,203/70,478 alleles

Filtering AF 3.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.97%

Overall 0.165% 2,499/1,518,396 alleles · low-frequency exomes 1,159/1,366,194 · genomes 1,340/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.13%	32
Remaining individualsnot grpmax-eligible	0.206%	484
Admixed American	0.196%	511
Middle Eastern	0.116%	861
South Asian	0.0109%	9,161
European (non-Finnish)	0.00526%	19,003
East Asian	0.00513%	19,511

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.Pro25Ser
Coding: c.73C>T
MANE Select: NM_000091
dbSNP: rs139271412
Type: single nucleotide variant
Location: chr2:227164799 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 48.64 · 2 PDB

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

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Alport syndrome

Similar variants

COL4A3 p.Pro25= Likely benign ★ same residue
COL4A3 c.1114+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>A 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
COL4A3 c.1927+1G>A Likely pathogenic ★★ same condition
COL4A3 c.2020+1G>T Likely pathogenic ★★ same condition
COL4A3 c.2224-2A>G 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-pro25ser (accessed [today's date]).

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