Is COL6A6 p.Ala67Val (c.200C>T) pathogenic?

COL6A6 p.Ala67Val (c.200C>T) is classified Uncertain significance in COL6A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). AlphaMissense: likely pathogenic (0.7254); Very rare (popmax 8.48e-05%, nfe).

How common is COL6A6 p.Ala67Val (c.200C>T) in the general population?

COL6A6 p.Ala67Val (c.200C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about COL6A6 p.Ala67Val (c.200C>T)?

AlphaMissense predicts likely pathogenic (score 0.7254) — an in-silico prediction, not a clinical call.

COL6A6 p.Ala67Val

c.200C>T · rs2062934727 · VCV2279596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7254 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7254	likely pathogenic
REVEL	0.563	indeterminate
SaProt	LLR -11.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -0.92, phastCons 0.21
Regional constraint	o/e 1.00	unconstrained · MANE · 115 kb · p 0.99 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,896 alleles

Overall 6.84e-05% 1/1,461,706 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: COL6A6
Protein: p.Ala67Val
Coding: c.200C>T
MANE Select: NM_001102608
dbSNP: rs2062934727
Type: single nucleotide variant
Location: chr3:130563203 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.61
Residue 67: the 'nonhelical region' region; the vwfa 1 domain

Full COL6A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL6A6 p.Arg1295Ter Uncertain significance ★★ same type
COL6A6 p.Arg1864Thr Uncertain significance ★★ same type
COL6A6 p.Arg906His Uncertain significance ★★ ⚠ same type
COL6A6 p.Arg937Trp Uncertain significance ★★ ⚠ same type
COL6A6 p.Tyr1805Cys Uncertain significance ★★ ⚠ same type
COL6A6 c.2977+4A>T Benign ★★ same type
COL6A6 c.4273-3C>T Likely benign ★★ same type
COL6A6 p.Ala1876= Benign ★★ 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/col6a6-p-ala67val (accessed [today's date]).

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