Is COL3A1 p.Pro575Ser (c.1723C>T) pathogenic?

COL3A1 p.Pro575Ser (c.1723C>T) is classified Uncertain significance in COL3A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). AlphaMissense: likely benign (0.2558); Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL3A1 p.Pro575Ser (c.1723C>T)?

COL3A1 p.Pro575Ser (c.1723C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL3A1 p.Pro575Ser (c.1723C>T) in the general population?

COL3A1 p.Pro575Ser (c.1723C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL3A1 p.Pro575Ser (c.1723C>T)?

AlphaMissense predicts likely benign (score 0.2558) — an in-silico prediction, not a clinical call.

COL3A1 p.Pro575Ser

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

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

c.1723C>T · rs1688321435 · VCV923142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2558 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.2558	likely benign
REVEL	0.715	pathogenic-leaning
SaProt	LLR -9.95	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Pangolin	Δ0.21	gain · loss 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 41 bp · p 2.8e-05 · regional, not allelic
Overall
CADD	28.9	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

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: COL3A1
Protein: p.Pro575Ser
Coding: c.1723C>T
MANE Select: NM_000090
dbSNP: rs1688321435
Type: single nucleotide variant
Location: chr2:188996458 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.98 · 11 PDB
Residue 575: a modified residue (4-hydroxyproline); a UniProt-annotated variant site (in pmgedsv); the 'disordered' region; the 'triple-helical region' region

Full COL3A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

COL3A1 p.Pro575Arg Uncertain significance ★★ ⚠ same residue
COL3A1 p.Pro575= Likely benign ★ same residue
COL3A1 c.1294-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.1347+1G>A Pathogenic ★★ same condition
COL3A1 c.1348-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL3A1 c.1662+1G>A Pathogenic ★★ same condition
COL3A1 c.2229+1G>A Likely pathogenic ★★ same condition
COL3A1 c.3093+1G>T 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/col3a1-p-pro575ser (accessed [today's date]).

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