Is COL7A1 p.Pro2191Leu (c.6572C>T) pathogenic?

COL7A1 p.Pro2191Leu (c.6572C>T) is classified Conflicting classifications of pathogenicity in COL7A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0884); Ultra-rare (popmax 0.0227%, afr); Associated with Inborn genetic diseases.

What condition is associated with COL7A1 p.Pro2191Leu (c.6572C>T)?

COL7A1 p.Pro2191Leu (c.6572C>T) is associated with Inborn genetic diseases, epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Pro2191Leu (c.6572C>T) in the general population?

COL7A1 p.Pro2191Leu (c.6572C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about COL7A1 p.Pro2191Leu (c.6572C>T)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro2191Leu

c.6572C>T · rs140543032 · VCV345818

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.526	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	24.4	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 0.0227% African / African-American · 17/74,876 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00236% 38/1,612,732 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,404
Admixed American	0.00335%	29,893
East Asian	0.00223%	44,844
European (non-Finnish)	0.00144%	69,378
South Asian	0.0011%	90,902

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.Pro2191Leu
Coding: c.6572C>T
MANE Select: NM_000094
dbSNP: rs140543032
Type: single nucleotide variant
Location: chr3:48573691 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 2191: 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

Also linked: epidermolysis bullosa dystrophica

Similar variants

COL7A1 p.Pro2191= Uncertain significance ★★ same residue
COL7A1 p.Pro2191Arg Uncertain significance ★ same residue
COL7A1 c.1637-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2587+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2587+40G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.266+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2710+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2992+2T>G Pathogenic ★★ 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-pro2191leu (accessed [today's date]).

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