Is COL1A2 p.Pro809Ser (c.2425C>T) pathogenic?

COL1A2 p.Pro809Ser (c.2425C>T) is classified Conflicting classifications of pathogenicity in COL1A2 (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0709); Ultra-rare (popmax 0.0235%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with COL1A2 p.Pro809Ser (c.2425C>T)?

COL1A2 p.Pro809Ser (c.2425C>T) is associated with Cardiovascular phenotype, connective tissue disorder, osteogenesis imperfecta type 1 (ClinVar).

How common is COL1A2 p.Pro809Ser (c.2425C>T) in the general population?

COL1A2 p.Pro809Ser (c.2425C>T) is ultra-rare (popmax 0.0235%, nfe) (gnomAD).

What do computational predictors say about COL1A2 p.Pro809Ser (c.2425C>T)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

COL1A2 p.Pro809Ser

c.2425C>T · rs145355907 · VCV431901

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0235%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -8.78	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.0235% European (non-Finnish) · 277/1,179,998 alleles

Filtering AF 0.0212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0203%

Overall 0.0217% 351/1,613,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.179%	559
Remaining individualsnot grpmax-eligible	0.024%	4,165
European (non-Finnish)grpmax	0.0235%	4,260
Admixed American	0.005%	20,001
Finnishnot grpmax-eligible	0.00312%	32,014
African / African-American	0.00134%	74,876

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL1A2
Protein: p.Pro809Ser
Coding: c.2425C>T
MANE Select: NM_000089
dbSNP: rs145355907
Type: single nucleotide variant
Location: chr7:94422978 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 809: a UniProt-annotated variant site (in oi2); the 'disordered' region

Full COL1A2 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

Also linked: connective tissue disorder osteogenesis imperfecta type 1 osteogenesis imperfecta Ehlers-Danlos syndrome, classic type, 1 Ehlers-Danlos syndrome, arthrochalasia type, 2

Similar variants

COL1A2 p.Pro809= Likely benign ★ same residue
COL1A2 p.Pro809Ala Uncertain significance ★ ⚠ same residue
COL1A2 p.Pro809His Uncertain significance ★ ⚠ same residue
COL1A2 c.1197+5G>A Pathogenic ★★ same condition
COL1A2 c.1503+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.1503+1G>C Pathogenic ★★ same condition
COL1A2 c.1557+3A>G Pathogenic ★★ same condition
COL1A2 c.2026-2A>G 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/col1a2-p-pro809ser (accessed [today's date]).

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