Is COL11A2 p.Met283Val (c.847A>G) pathogenic?

COL11A2 p.Met283Val (c.847A>G) is classified Uncertain significance in COL11A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-11). AlphaMissense: likely benign (0.1141); Absent from gnomAD v4.1.

How common is COL11A2 p.Met283Val (c.847A>G) in the general population?

COL11A2 p.Met283Val (c.847A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL11A2 p.Met283Val (c.847A>G)?

AlphaMissense predicts likely benign (score 0.1141) — an in-silico prediction, not a clinical call.

COL11A2 p.Met283Val

c.847A>G · rs2535477293 · VCV2501547

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1141	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -4.27	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 3.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	16.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: COL11A2
Protein: p.Met283Val
Coding: c.847A>G
MANE Select: NM_080680
dbSNP: rs2535477293
Type: single nucleotide variant
Location: chr6:33185730 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 283: the 'nonhelical region' region; the 'disordered' region

Full COL11A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL11A2 c.1119+1G>A Likely pathogenic ★★ same type
COL11A2 c.1819-2A>G Likely pathogenic ★★ same type
COL11A2 c.3852+1G>T Likely pathogenic ★★ same type
COL11A2 c.4392+1G>A Pathogenic ★★ same type
COL11A2 c.607-2A>T Likely pathogenic ★★ same type
COL11A2 c.876+1G>A Likely pathogenic ★★ same type
COL11A2 p.Arg1020Ter Pathogenic/Likely pathogenic ★★ same type
COL11A2 p.Arg1034Cys Pathogenic/Likely pathogenic ★★ ⚠ same type

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/col11a2-p-met283val (accessed [today's date]).

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