Is COL11A2 p.Ser1630Phe (c.4889C>T) pathogenic?

COL11A2 p.Ser1630Phe (c.4889C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-07). AlphaMissense: likely benign (0.1142); Very rare (popmax 0.00184%, amr); Associated with Inborn genetic diseases.

What condition is associated with COL11A2 p.Ser1630Phe (c.4889C>T)?

COL11A2 p.Ser1630Phe (c.4889C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL11A2 p.Ser1630Phe (c.4889C>T) in the general population?

COL11A2 p.Ser1630Phe (c.4889C>T) is very rare (popmax 0.00184%, amr) (gnomAD).

What do computational predictors say about COL11A2 p.Ser1630Phe (c.4889C>T)?

AlphaMissense predicts likely benign (score 0.1142) — an in-silico prediction, not a clinical call.

COL11A2 p.Ser1630Phe

c.4889C>T · rs773575924 · VCV1361179

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1142 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00184%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1142	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -9.28	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 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	23.8	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 0.00184% Admixed American · 1/54,298 alleles

Overall 7.05e-05% 1/1,419,280 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: COL11A2
Protein: p.Ser1630Phe
Coding: c.4889C>T
MANE Select: NM_080680
dbSNP: rs773575924
Type: single nucleotide variant
Location: chr6:33164448 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1630: the fibrillar collagen nc1 domain; a disulfide bond

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-ser1630phe (accessed [today's date]).

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