Is COL11A1 p.Pro331Ser (c.991C>T) pathogenic?

COL11A1 p.Pro331Ser (c.991C>T) is classified Uncertain significance in COL11A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely benign (0.0733); Very rare (popmax 0.00667%, amr).

How common is COL11A1 p.Pro331Ser (c.991C>T) in the general population?

COL11A1 p.Pro331Ser (c.991C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about COL11A1 p.Pro331Ser (c.991C>T)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

COL11A1 p.Pro331Ser

c.991C>T · rs767032677 · VCV1911139

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -7.08	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 230 kb · p 0.038 · regional, not allelic
Overall
CADD	23.7	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 0.00667% Admixed American · 4/59,978 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00031% 5/1,611,338 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,995
European (non-Finnish)	8.48e-05%	1,178,807

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.Pro331Ser
Coding: c.991C>T
MANE Select: NM_001854
dbSNP: rs767032677
Type: single nucleotide variant
Location: chr1:103022996 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 331: the 'nonhelical region' region

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

Similar variants

COL11A1 p.Pro331Leu Uncertain significance ★★ ⚠ same residue
COL11A1 c.1245+1G>A Pathogenic/Likely pathogenic ★★ same type
COL11A1 c.1245+1G>T Pathogenic/Likely pathogenic ★★ same type
COL11A1 c.1629+1G>A Likely pathogenic ★★ same type
COL11A1 c.1630-1G>T Pathogenic ★★ same type
COL11A1 c.1791+1G>T Likely pathogenic ★★ same type
COL11A1 c.1900-1G>A Likely pathogenic ★★ same type
COL11A1 c.2241+5G>T Pathogenic/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/col11a1-p-pro331ser (accessed [today's date]).

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