Is COL1A2 p.Ala279= (c.837C>T) pathogenic?

COL1A2 p.Ala279= (c.837C>T) is classified Likely benign in COL1A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-09). Very rare (popmax 0.00934%, afr); Associated with Cardiovascular phenotype.

What condition is associated with COL1A2 p.Ala279= (c.837C>T)?

COL1A2 p.Ala279= (c.837C>T) is associated with Cardiovascular phenotype, osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Ala279= (c.837C>T) in the general population?

COL1A2 p.Ala279= (c.837C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

COL1A2 p.Ala279=

c.837C>T · rs1009671128 · VCV1763144

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.6	GERP -4.4
Overall
CADD	2.177	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,918 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00242% 39/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,703
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,902
Finnishnot grpmax-eligible	0.00156%	64,030

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.Ala279=
Coding: c.837C>T
MANE Select: NM_000089
dbSNP: rs1009671128
Type: single nucleotide variant
Location: chr7:94409366 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 279: 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: osteogenesis imperfecta type 1 Ehlers-Danlos syndrome, classic type, 1

Similar variants

COL1A2 p.Ala279Pro Uncertain significance ★★ ⚠ same residue
COL1A2 p.Ala279Thr Uncertain significance ★★ ⚠ same residue
COL1A2 p.Ala279Gly 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-ala279 (accessed [today's date]).

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