Is COL6A2 p.Pro471Ser (c.1411C>T) pathogenic?

COL6A2 p.Pro471Ser (c.1411C>T) is classified Uncertain significance in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.2045); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL6A2 p.Pro471Ser (c.1411C>T)?

COL6A2 p.Pro471Ser (c.1411C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL6A2 p.Pro471Ser (c.1411C>T) in the general population?

COL6A2 p.Pro471Ser (c.1411C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about COL6A2 p.Pro471Ser (c.1411C>T)?

AlphaMissense predicts likely benign (score 0.2045) — an in-silico prediction, not a clinical call.

COL6A2 p.Pro471Ser

c.1411C>T · VCV4005500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2045	likely benign
REVEL	0.654	pathogenic-leaning
SaProt	LLR -8.39	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.3, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 16 kb · p 1.4e-07 · regional, not allelic
Overall
CADD	25.3	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 8.48e-05% European (non-Finnish) · 1/1,179,918 alleles

Overall 6.85e-05% 1/1,460,500 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: COL6A2
Protein: p.Pro471Ser
Coding: c.1411C>T
MANE Select: NM_001849
Type: single nucleotide variant
Location: chr21:46121076 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 471: the 'triple-helical region' region; the 'disordered' region

Full COL6A2 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

COL6A2 c.955-2A>G Pathogenic ★★ same condition
COL6A2 p.Glu668Ter Pathogenic ★★ same condition
COL6A2 p.Ala1006Thr Uncertain significance ★★ ⚠ same condition
COL6A2 p.Ala139Ser Uncertain significance ★★ ⚠ same condition
COL6A2 p.Ala191Val Uncertain significance ★★ ⚠ same condition
COL6A2 p.Ala389Ser Uncertain significance ★★ ⚠ same condition
COL6A2 p.Ala673Asp Uncertain significance ★★ ⚠ same condition
COL6A2 p.Ala904Thr 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/col6a2-p-pro471ser (accessed [today's date]).

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