Is COL2A1 p.Val905Ala (c.2714T>C) pathogenic?

COL2A1 p.Val905Ala (c.2714T>C) is classified Conflicting classifications of pathogenicity in COL2A1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-14). AlphaMissense: ambiguous (0.449); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COL2A1 p.Val905Ala (c.2714T>C)?

COL2A1 p.Val905Ala (c.2714T>C) is associated with Inborn genetic diseases (ClinVar).

How common is COL2A1 p.Val905Ala (c.2714T>C) in the general population?

COL2A1 p.Val905Ala (c.2714T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL2A1 p.Val905Ala (c.2714T>C)?

AlphaMissense predicts ambiguous (score 0.449) — an in-silico prediction, not a clinical call.

COL2A1 p.Val905Ala

c.2714T>C · rs1271505111 · VCV1224439

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.449 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.449	ambiguous
REVEL	0.557	indeterminate
SaProt	LLR -4.76	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.69, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 21 kb · p 2.4e-45 · regional, not allelic
Overall
CADD	24.8	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

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: COL2A1
Protein: p.Val905Ala
Coding: c.2714T>C
MANE Select: NM_001844
dbSNP: rs1271505111
Type: single nucleotide variant
Location: chr12:47979530 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 905: the 'disordered' region; the 'triple-helical region' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL2A1 p.Val905Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
COL2A1 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Gln39Ter Pathogenic ★★ same condition
COL2A1 p.Gly546Ser Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Gly930Asp Likely pathogenic ★★ same condition
COL2A1 p.Ala1093Val Uncertain significance ★★ ⚠ same condition
COL2A1 p.Ala180Thr Uncertain significance ★★ ⚠ same condition
COL2A1 p.Ala559Ser 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/col2a1-p-val905ala (accessed [today's date]).

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