Is COL7A1 p.Pro2215Ala (c.6643C>G) pathogenic?

COL7A1 p.Pro2215Ala (c.6643C>G) is classified Uncertain significance in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0567); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with COL7A1 p.Pro2215Ala (c.6643C>G)?

COL7A1 p.Pro2215Ala (c.6643C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL7A1 p.Pro2215Ala (c.6643C>G) in the general population?

COL7A1 p.Pro2215Ala (c.6643C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about COL7A1 p.Pro2215Ala (c.6643C>G)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro2215Ala

c.6643C>G · rs1489201304 · VCV1478377

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.411	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	20.9	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 6.84e-05%

Overall 6.84e-05% 1/1,461,744 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: COL7A1
Protein: p.Pro2215Ala
Coding: c.6643C>G
MANE Select: NM_000094
dbSNP: rs1489201304
Type: single nucleotide variant
Location: chr3:48573324 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 2215: the 'triple-helical region' region; the 'disordered' region

Full COL7A1 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

COL7A1 p.Pro2215Gln Uncertain significance ★ same residue
COL7A1 p.Pro2215Ser Uncertain significance ★ same residue
COL7A1 p.Ala1282Thr Uncertain significance ★★ ⚠ same condition
COL7A1 p.Ala2258Thr Uncertain significance ★★ ⚠ same condition
COL7A1 p.Ala2328Gly Uncertain significance ★★ same condition
COL7A1 p.Ala2513Val Uncertain significance ★★ ⚠ same condition
COL7A1 p.Ala2592Glu Uncertain significance ★★ same condition
COL7A1 p.Ala36Thr 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/col7a1-p-pro2215ala (accessed [today's date]).

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