Is COL11A2 p.Ala27Val (c.80C>T) pathogenic?

COL11A2 p.Ala27Val (c.80C>T) is classified Uncertain significance in COL11A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). AlphaMissense: likely benign (0.1872); Absent from gnomAD v4.1.

How common is COL11A2 p.Ala27Val (c.80C>T) in the general population?

COL11A2 p.Ala27Val (c.80C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL11A2 p.Ala27Val (c.80C>T)?

AlphaMissense predicts likely benign (score 0.1872) — an in-silico prediction, not a clinical call.

COL11A2 p.Ala27Val

c.80C>T · rs1773196594 · VCV2699803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1872 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,556,694)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1872	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.97	donor gain · deltas
Pangolin	Δ0.65	gain · loss 0.41 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	35.0	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

No allele count reported in gnomAD v4.1 (AN 1,556,694). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL11A2
Protein: p.Ala27Val
Coding: c.80C>T
MANE Select: NM_080680
dbSNP: rs1773196594
Type: single nucleotide variant
Location: chr6:33192161 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18

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

Similar variants

COL11A2 p.Ala27Pro Uncertain significance ★★ ⚠ same residue
COL11A2 p.Ala27Thr Uncertain significance ★ ⚠ same residue
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

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-ala27val (accessed [today's date]).

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