Is COL6A1 p.Ala856Ser (c.2566G>T) pathogenic?

COL6A1 p.Ala856Ser (c.2566G>T) is classified Uncertain significance in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.1458); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COL6A1 p.Ala856Ser (c.2566G>T)?

COL6A1 p.Ala856Ser (c.2566G>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL6A1 p.Ala856Ser (c.2566G>T) in the general population?

COL6A1 p.Ala856Ser (c.2566G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL6A1 p.Ala856Ser (c.2566G>T)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

COL6A1 p.Ala856Ser

c.2566G>T · rs2526354100 · VCV2265647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,510)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.77, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	20.5	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

No allele count reported in gnomAD v4.1 (AN 1,610,510). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL6A1
Protein: p.Ala856Ser
Coding: c.2566G>T
MANE Select: NM_001848
dbSNP: rs2526354100
Type: single nucleotide variant
Location: chr21:46003492 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 856: the vwfa 3 domain; the 'c-terminal globular domain' region

Full COL6A1 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

COL6A1 p.Ala856= Likely benign ★★ same residue
COL6A1 p.Ala856Thr Uncertain significance ★ ⚠ same residue
COL6A1 p.Gly275Val Pathogenic/Likely pathogenic ★★ same condition
COL6A1 p.Ala216Ser Uncertain significance ★★ ⚠ same condition
COL6A1 p.Ala698Val Uncertain significance ★★ ⚠ same condition
COL6A1 p.Arg424Trp Uncertain significance ★★ ⚠ same condition
COL6A1 p.Arg711Trp Uncertain significance ★★ ⚠ same condition
COL6A1 p.Asp21His 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/col6a1-p-ala856ser (accessed [today's date]).

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