Is COL2A1 p.Ala1177Ser (c.3529G>T) pathogenic?

COL2A1 p.Ala1177Ser (c.3529G>T) is classified Likely benign in COL2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0575); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COL2A1 p.Ala1177Ser (c.3529G>T)?

COL2A1 p.Ala1177Ser (c.3529G>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL2A1 p.Ala1177Ser (c.3529G>T) in the general population?

COL2A1 p.Ala1177Ser (c.3529G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL2A1 p.Ala1177Ser (c.3529G>T)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

COL2A1 p.Ala1177Ser

c.3529G>T · VCV4005340

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -7.83	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 0.91	GERP -3.7, phastCons 0.16
Regional constraint	o/e 0.62	unconstrained · MANE · 21 kb · p 2.4e-45 · regional, not allelic
Overall
CADD	11.56	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL2A1
Protein: p.Ala1177Ser
Coding: c.3529G>T
MANE Select: NM_001844
Type: single nucleotide variant
Location: chr12:47976031 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 1177: a UniProt-annotated variant site (in sedc); the 'disordered' region; the 'triple-helical region' region

Full COL2A1 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

COL2A1 p.Ala1177Gly Uncertain significance ★ ⚠ same residue
COL2A1 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Gln39Ter Pathogenic ★★ same condition
COL2A1 p.Gly546Ser Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Gly930Asp Likely pathogenic ★★ same condition
COL2A1 p.Ala1093Val Uncertain significance ★★ ⚠ same condition
COL2A1 p.Ala180Thr Uncertain significance ★★ ⚠ same condition
COL2A1 p.Ala559Ser 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/col2a1-p-ala1177ser (accessed [today's date]).

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