Is COL4A3 p.Pro362Ser (c.1084C>T) pathogenic?

COL4A3 p.Pro362Ser (c.1084C>T) is classified Uncertain significance in COL4A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-11). AlphaMissense: likely benign (0.097); Very rare (popmax 0.000848%, nfe); Associated with autosomal dominant Alport syndrome.

What condition is associated with COL4A3 p.Pro362Ser (c.1084C>T)?

COL4A3 p.Pro362Ser (c.1084C>T) is associated with autosomal dominant Alport syndrome, hematuria, benign familial (ClinVar).

How common is COL4A3 p.Pro362Ser (c.1084C>T) in the general population?

COL4A3 p.Pro362Ser (c.1084C>T) is very rare (popmax 0.000848%, nfe) (gnomAD).

How is Alport syndrome inherited?

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

What do computational predictors say about COL4A3 p.Pro362Ser (c.1084C>T)?

AlphaMissense predicts likely benign (score 0.097) — an in-silico prediction, not a clinical call.

COL4A3 p.Pro362Ser

c.1084C>T · rs767943108 · VCV870360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal dominant Alport syndrome

Computational evidence

Protein change
AlphaMissense	0.097	likely benign
REVEL	0.633	indeterminate
SaProt	LLR -9.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 0.17
Regional constraint	o/e 0.84	unconstrained · MANE · 58 kb · p 2.1e-11 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,516 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 10/1,461,278 alleles · very rare

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.Pro362Ser
Coding: c.1084C>T
dbSNP: rs767943108
Type: single nucleotide variant
Location: chr2:227259847 (GRCh38)

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: hematuria, benign familial

For Alport syndrome (Orphanet):

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

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-pro362ser (accessed [today's date]).

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