Is COL11A2 p.Ile1506Val (c.4516A>G) pathogenic?

COL11A2 p.Ile1506Val (c.4516A>G) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-16). AlphaMissense: likely benign (0.2482); Ultra-rare (popmax 0.0132%, sas); Associated with Inborn genetic diseases.

What condition is associated with COL11A2 p.Ile1506Val (c.4516A>G)?

COL11A2 p.Ile1506Val (c.4516A>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL11A2 p.Ile1506Val (c.4516A>G) in the general population?

COL11A2 p.Ile1506Val (c.4516A>G) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about COL11A2 p.Ile1506Val (c.4516A>G)?

AlphaMissense predicts likely benign (score 0.2482) — an in-silico prediction, not a clinical call.

COL11A2 p.Ile1506Val

c.4516A>G · rs772312309 · VCV1392503

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2482 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2482	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	21.2	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 0.0132% South Asian · 12/91,060 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.0011% 16/1,461,168 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,588
Remaining individualsnot grpmax-eligible	0.0064%	15,624

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.Ile1506Val
Coding: c.4516A>G
MANE Select: NM_080680
dbSNP: rs772312309
Type: single nucleotide variant
Location: chr6:33165783 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1506: the 'disordered' region

Full COL11A2 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

COL11A2 p.Ala216Glu Uncertain significance ★★ ⚠ same condition
COL11A2 p.Ala66Pro Uncertain significance ★★ ⚠ same condition
COL11A2 p.Ala827Gly Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg1596Gln Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg1667Ser Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg36Gln Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg729Trp Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg73Leu 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/col11a2-p-ile1506val (accessed [today's date]).

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