Is COL11A2 p.Asp1618= (c.4854C>T) pathogenic?

COL11A2 p.Asp1618= (c.4854C>T) is classified Benign/Likely benign in COL11A2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-18). Rare (popmax 0.172%, sas); Associated with connective tissue disorder.

What condition is associated with COL11A2 p.Asp1618= (c.4854C>T)?

COL11A2 p.Asp1618= (c.4854C>T) is associated with connective tissue disorder (ClinVar).

How common is COL11A2 p.Asp1618= (c.4854C>T) in the general population?

COL11A2 p.Asp1618= (c.4854C>T) is rare (popmax 0.172%, sas) (gnomAD).

COL11A2 p.Asp1618=

c.4854C>T · rs151319255 · VCV1203248

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, sas)

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.3
Overall
CADD	0.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% South Asian · 146/84,688 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.0134% 209/1,560,116 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.172%	580
Middle Eastern	0.0167%	6,000
Remaining individualsnot grpmax-eligible	0.00662%	15,114
East Asian	0.00476%	21,007
European (non-Finnish)	0.00469%	21,316
Admixed American	0.00382%	26,144

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.Asp1618=
Coding: c.4854C>T
MANE Select: NM_080680
dbSNP: rs151319255
Type: single nucleotide variant
Location: chr6:33164861 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1618: the fibrillar collagen nc1 domain; a disulfide bond

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL11A2 p.Asp1618Glu Uncertain significance ★ ⚠ same residue
COL11A2 p.Arg876Met Uncertain significance ★★ ⚠ same condition
COL11A2 p.Pro524Ser Uncertain significance ★★ ⚠ same condition
COL11A2 c.1284+8G>A Likely benign ★★ same condition
COL11A2 c.1446+19C>T Likely benign ★★ same condition
COL11A2 c.1612-16T>A Likely benign ★★ same condition
COL11A2 c.3475-19G>A Likely benign ★★ same condition
COL11A2 c.3583-5T>C Benign/Likely benign ★★ 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-asp1618 (accessed [today's date]).

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