Is COL3A1 p.Ser1237Leu (c.3710C>T) pathogenic?

COL3A1 p.Ser1237Leu (c.3710C>T) is classified Uncertain significance in COL3A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-10). AlphaMissense: ambiguous (0.4373); Absent from gnomAD v4.1; Associated with Ehlers-Danlos syndrome, vascular type.

What condition is associated with COL3A1 p.Ser1237Leu (c.3710C>T)?

COL3A1 p.Ser1237Leu (c.3710C>T) is associated with Ehlers-Danlos syndrome, vascular type (ClinVar).

How common is COL3A1 p.Ser1237Leu (c.3710C>T) in the general population?

COL3A1 p.Ser1237Leu (c.3710C>T) is absent from gnomAD v4.1 (gnomAD).

How is Vascular Ehlers-Danlos syndrome inherited?

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

What do computational predictors say about COL3A1 p.Ser1237Leu (c.3710C>T)?

AlphaMissense predicts ambiguous (score 0.4373) — an in-silico prediction, not a clinical call.

COL3A1 p.Ser1237Leu

c.3710C>T · rs985651774 · VCV2759534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4373 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Ehlers-Danlos syndrome, vascular type

Computational evidence

Protein change
AlphaMissense	0.4373	ambiguous
REVEL	0.695	pathogenic-leaning
SaProt	LLR -7.87	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 15 kb · p 5.1e-19 · regional, not allelic
Overall
CADD	26.2	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.Ser1237Leu
Coding: c.3710C>T
MANE Select: NM_000090
dbSNP: rs985651774
Type: single nucleotide variant
Location: chr2:189009108 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.98 · 11 PDB
Residue 1237: a UniProt-annotated variant site (in pmgedsv); an α-helix; the fibrillar collagen nc1 domain

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

Disease context

Ehlers-Danlos syndrome, vascular type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Vascular Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

COL3A1 c.1051-1G>C Likely pathogenic ★★ same condition
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.1663-1G>A Likely pathogenic ★★ same condition
COL3A1 c.1869+1G>C Pathogenic ★★ same condition
COL3A1 c.2229+1G>A 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-ser1237leu (accessed [today's date]).

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