Is COL1A2 p.Val294Phe (c.880G>T) pathogenic?

COL1A2 p.Val294Phe (c.880G>T) is classified Conflicting classifications of pathogenicity in COL1A2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1956); Rare (popmax 0.175%, afr); Associated with Ehlers-Danlos syndrome.

What condition is associated with COL1A2 p.Val294Phe (c.880G>T)?

COL1A2 p.Val294Phe (c.880G>T) is associated with Ehlers-Danlos syndrome, osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Val294Phe (c.880G>T) in the general population?

COL1A2 p.Val294Phe (c.880G>T) is rare (popmax 0.175%, afr) (gnomAD).

What do computational predictors say about COL1A2 p.Val294Phe (c.880G>T)?

AlphaMissense predicts likely benign (score 0.1956) — an in-silico prediction, not a clinical call.

COL1A2 p.Val294Phe

c.880G>T · rs145693444 · VCV772979

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1956 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.175%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Ehlers-Danlos syndrome

Computational evidence

Protein change
AlphaMissense	0.1956	likely benign
REVEL	0.606	indeterminate
SaProt	LLR -11.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	23.8	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 0.175% African / African-American · 131/75,042 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.00954% 154/1,614,160 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.175%	573
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Middle Eastern	0.0165%	6,062
Admixed American	0.015%	6,668
European (non-Finnish)	0.000169%	590,009

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.Val294Phe
Coding: c.880G>T
MANE Select: NM_000089
dbSNP: rs145693444
Type: single nucleotide variant
Location: chr7:94409409 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 294: the 'disordered' region

Full COL1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome — 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.Val294Ile Uncertain significance ★★ ⚠ same residue
COL1A2 c.1197+5G>A Pathogenic ★★ same condition
COL1A2 c.1404+1G>A Pathogenic/Likely 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
COL1A2 c.2133+6T>A 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-val294phe (accessed [today's date]).

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