Is COL11A1 p.Pro396Ser (c.1186C>T) pathogenic?

COL11A1 p.Pro396Ser (c.1186C>T) is classified Uncertain significance in COL11A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-03). AlphaMissense: likely benign (0.0601); Very rare (popmax 0.0011%, sas); Associated with COL11A1-related disorder.

What condition is associated with COL11A1 p.Pro396Ser (c.1186C>T)?

COL11A1 p.Pro396Ser (c.1186C>T) is associated with COL11A1-related disorder (ClinVar).

How common is COL11A1 p.Pro396Ser (c.1186C>T) in the general population?

COL11A1 p.Pro396Ser (c.1186C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about COL11A1 p.Pro396Ser (c.1186C>T)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

COL11A1 p.Pro396Ser

c.1186C>T · rs2525581497 · VCV2632889

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COL11A1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -1.9, phastCons 0.097
Regional constraint	o/e 0.96	unconstrained · MANE · 230 kb · p 0.038 · regional, not allelic
Overall
CADD	12.07	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 0.0011% South Asian · 1/91,068 alleles

Overall 6.84e-05% 1/1,461,438 alleles · very rare

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: COL11A1
Protein: p.Pro396Ser
Coding: c.1186C>T
MANE Select: NM_001854
dbSNP: rs2525581497
Type: single nucleotide variant
Location: chr1:103022801 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 396: the 'nonhelical region' region

Full COL11A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL11A1-related disorder

Similar variants

COL11A1 p.Pro396= Likely benign ★ same residue
COL11A1 c.3816+1G>A Pathogenic ★★ same condition
COL11A1 c.3978+2T>G Likely pathogenic ★★ same condition
COL11A1 c.4519-2A>G Pathogenic ★★ same condition
COL11A1 p.Arg1362Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A1 p.Glu335Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A1 p.Gly838Glu Pathogenic/Likely pathogenic ★★ same condition
COL11A1 p.Gly841Val Likely pathogenic ★★ 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/col11a1-p-pro396ser (accessed [today's date]).

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