Is COL5A1 p.Ser68Pro (c.202T>C) pathogenic?

COL5A1 p.Ser68Pro (c.202T>C) is classified Uncertain significance in COL5A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-07). AlphaMissense: likely benign (0.1851); Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with COL5A1 p.Ser68Pro (c.202T>C)?

COL5A1 p.Ser68Pro (c.202T>C) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is COL5A1 p.Ser68Pro (c.202T>C) in the general population?

COL5A1 p.Ser68Pro (c.202T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL5A1 p.Ser68Pro (c.202T>C)?

AlphaMissense predicts likely benign (score 0.1851) — an in-silico prediction, not a clinical call.

COL5A1 p.Ser68Pro

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.202T>C · rs1554780172 · VCV519644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.1851	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -9.67	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 3.3	GERP -1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 96 kb · p 0.17 · regional, not allelic
Overall
CADD	22.1	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: COL5A1
Protein: p.Ser68Pro
Coding: c.202T>C
MANE Select: NM_000093
dbSNP: rs1554780172
Type: single nucleotide variant
Location: chr9:134691004 (GRCh38)
Gene constraint: LOEUF 0.089 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.54 · 1 PDB

Full COL5A1 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

COL5A1 p.Ser68Cys Uncertain significance ★ ⚠ same residue
COL5A1 c.1720-11T>A Likely pathogenic ★★ same condition
COL5A1 c.655-1G>C Likely pathogenic ★★ same condition
COL5A1 c.655-2A>T Likely pathogenic ★★ same condition
COL5A1 p.Arg1062Ter Pathogenic ★★ same condition
COL5A1 p.Arg594Ter Pathogenic/Likely pathogenic ★★ same condition
COL5A1 p.Arg912Ter Pathogenic ★★ same condition
COL5A1 c.1828-3C>G Uncertain significance ★★ 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/col5a1-p-ser68pro (accessed [today's date]).

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