Is COL11A2 p.Ala481Val (c.1442C>T) pathogenic?

COL11A2 p.Ala481Val (c.1442C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.5945); Very rare (popmax 0.00167%, amr).

How common is COL11A2 p.Ala481Val (c.1442C>T) in the general population?

COL11A2 p.Ala481Val (c.1442C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about COL11A2 p.Ala481Val (c.1442C>T)?

AlphaMissense predicts likely pathogenic (score 0.5945) — an in-silico prediction, not a clinical call.

COL11A2 p.Ala481Val

c.1442C>T · rs749620886 · VCV2146979

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.5945 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5945	likely pathogenic
REVEL	0.69	pathogenic-leaning
SaProt	LLR -5.13	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.92	donor gain · deltas
Pangolin	Δ0.82	gain · loss 0.25 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.7, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Overall 0.000248% 4/1,611,614 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,468
South Asian	0.0011%	91,062
European (non-Finnish)	8.47e-05%	1,179,956

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: COL11A2
Protein: p.Ala481Val
Coding: c.1442C>T
MANE Select: NM_080680
dbSNP: rs749620886
Type: single nucleotide variant
Location: chr6:33179723 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 481: the 'nonhelical region' region

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

Similar variants

COL11A2 p.Ala481= Likely benign ★★ same residue
COL11A2 p.Ala481Thr 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-ala481val (accessed [today's date]).

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