Is COL4A3 p.Pro272Ser (c.814C>T) pathogenic?

COL4A3 p.Pro272Ser (c.814C>T) is classified Uncertain significance in COL4A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0772); Absent from gnomAD v4.1; Associated with autosomal recessive Alport syndrome.

What condition is associated with COL4A3 p.Pro272Ser (c.814C>T)?

COL4A3 p.Pro272Ser (c.814C>T) is associated with autosomal recessive Alport syndrome, autosomal dominant Alport syndrome (ClinVar).

How common is COL4A3 p.Pro272Ser (c.814C>T) in the general population?

COL4A3 p.Pro272Ser (c.814C>T) is absent from gnomAD v4.1 (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.Pro272Ser (c.814C>T)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

COL4A3 p.Pro272Ser

c.814C>T · rs2469568805 · VCV2443033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive Alport syndrome

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.6, phastCons 0.99
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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL4A3
Protein: p.Pro272Ser
Coding: c.814C>T
MANE Select: NM_000091
dbSNP: rs2469568805
Type: single nucleotide variant
Location: chr2:227254160 (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 272: 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 recessive Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant Alport syndrome

For Alport syndrome (Orphanet):

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

Similar variants

COL4A3 p.Pro272Leu Uncertain significance ★ ⚠ 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
COL4A3 c.2489-1G>A Likely pathogenic ★★ same condition
COL4A3 c.2656+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.2746+1G>T 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-pro272ser (accessed [today's date]).

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