Is COL11A2 p.Ala1122Val (c.3365C>T) pathogenic?

COL11A2 p.Ala1122Val (c.3365C>T) is classified Uncertain significance in COL11A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-09-17). AlphaMissense: likely benign (0.1792); Ultra-rare (popmax 0.0334%, mid).

How common is COL11A2 p.Ala1122Val (c.3365C>T) in the general population?

COL11A2 p.Ala1122Val (c.3365C>T) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

What do computational predictors say about COL11A2 p.Ala1122Val (c.3365C>T)?

AlphaMissense predicts likely benign (score 0.1792) — an in-silico prediction, not a clinical call.

COL11A2 p.Ala1122Val

c.3365C>T · rs748271072 · VCV1309169

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1792 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1792	likely benign
REVEL	0.527	indeterminate
SaProt	LLR -7.25	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 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.0334% Middle Eastern · 2/5,988 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.0134% 211/1,579,344 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0334%	2,994
Remaining individualsnot grpmax-eligible	0.0229%	4,376
European (non-Finnish)	0.0164%	6,114
Ashkenazi Jewishnot grpmax-eligible	0.00345%	28,990
African / African-American	0.0027%	37,095
Admixed American	0.00187%	53,426
South Asian	0.00114%	87,938

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.Ala1122Val
Coding: c.3365C>T
MANE Select: NM_080680
dbSNP: rs748271072
Type: single nucleotide variant
Location: chr6:33171115 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1122: the 'disordered' region; the 'triple-helical region' region; the collagen-like 6 domain

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

Similar variants

COL11A2 p.Ala1122= Uncertain significance ★★ same residue
COL11A2 p.Ala1122Gly 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-ala1122val (accessed [today's date]).

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