Is COL11A2 p.Leu271= (c.813C>T) pathogenic?

COL11A2 p.Leu271= (c.813C>T) is classified Likely benign in COL11A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0485%, nfe); Associated with connective tissue disorder.

What condition is associated with COL11A2 p.Leu271= (c.813C>T)?

COL11A2 p.Leu271= (c.813C>T) is associated with connective tissue disorder (ClinVar).

How common is COL11A2 p.Leu271= (c.813C>T) in the general population?

COL11A2 p.Leu271= (c.813C>T) is ultra-rare (popmax 0.0485%, nfe) (gnomAD).

COL11A2 p.Leu271=

c.813C>T · rs143505163 · VCV561281

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0485%, nfe)

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 6.8	GERP 0.46, phastCons 1
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0485% European (non-Finnish) · 489/1,009,264 alleles

Filtering AF 0.0449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0434%

Overall 0.0374% 506/1,351,152 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0485%	2,064
Remaining individualsnot grpmax-eligible	0.0263%	3,796
African / African-American	0.00749%	13,359

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.Leu271=
Coding: c.813C>T
MANE Select: NM_080680
dbSNP: rs143505163
Type: single nucleotide variant
Location: chr6:33185764 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 271: the 'nonhelical region' region; the 'disordered' region

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.Leu271Arg Conflicting classifications of pathogenicity ★ ⚠ 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-leu271 (accessed [today's date]).

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