Is COL1A1 p.Pro652= (c.1956A>T) pathogenic?

COL1A1 p.Pro652= (c.1956A>T) is classified Likely benign in COL1A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with COL1A1 p.Pro652= (c.1956A>T)?

COL1A1 p.Pro652= (c.1956A>T) is associated with Cardiovascular phenotype (ClinVar).

How common is COL1A1 p.Pro652= (c.1956A>T) in the general population?

COL1A1 p.Pro652= (c.1956A>T) is absent from gnomAD v4.1 (gnomAD).

COL1A1 p.Pro652=

c.1956A>T · VCV3495219

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.6	GERP -3.8
Overall
CADD	0.099	PHRED · no single calibrated threshold — expert panels disagree

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: COL1A1
Protein: p.Pro652=
Coding: c.1956A>T
MANE Select: NM_000088
Type: single nucleotide variant
Location: chr17:50192502 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.26 · 14 PDB
Residue 652: a modified residue (4-hydroxyproline); the 'disordered' region; the 'triple-helical region' region

Full COL1A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A1 c.1299+5G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 p.Arg1141Ter Pathogenic ★★ same condition
COL1A1 p.Gly188Asp Pathogenic/Likely pathogenic ★★ same condition
COL1A1 p.Gly200Val Pathogenic/Likely pathogenic ★★ same condition
COL1A1 p.Met181Ile Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.1056+3G>A Uncertain significance ★★ same condition
COL1A1 c.1822-3C>A Uncertain significance ★★ same condition
COL1A1 c.1876-3C>T 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/col1a1-p-pro652 (accessed [today's date]).

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