Is COL7A1 p.Pro1940= (c.5820G>A) pathogenic?

COL7A1 p.Pro1940= (c.5820G>A) is classified Pathogenic/Likely pathogenic in COL7A1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.0183%, amr); Associated with nonsyndromic congenital nail disorder 8.

What condition is associated with COL7A1 p.Pro1940= (c.5820G>A)?

COL7A1 p.Pro1940= (c.5820G>A) is associated with nonsyndromic congenital nail disorder 8, epidermolysis bullosa dystrophica, transient bullous dermolysis of the newborn (ClinVar).

How common is COL7A1 p.Pro1940= (c.5820G>A) in the general population?

COL7A1 p.Pro1940= (c.5820G>A) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

COL7A1 p.Pro1940=

c.5820G>A · rs200972872 · VCV431810

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

nonsyndromic congenital nail disorder 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.54	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.56	GERP 1, phastCons 0.089
Overall
CADD	18.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,008 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.0112% 181/1,613,548 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.024%	4,164
Admixed Americangrpmax	0.0183%	5,455
Middle Eastern	0.0167%	6,004
European (non-Finnish)	0.0127%	7,867
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,445
South Asian	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1940=
Coding: c.5820G>A
MANE Select: NM_000094
dbSNP: rs200972872
Type: single nucleotide variant
Location: chr3:48576249 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 1940: the 'disordered' region; the 'triple-helical region' region

Full COL7A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nonsyndromic congenital nail disorder 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa dystrophica transient bullous dermolysis of the newborn generalized dominant dystrophic epidermolysis bullosa pretibial dystrophic epidermolysis bullosa epidermolysis bullosa with congenital localized absence of skin and deformity of nails recessive dystrophic epidermolysis bullosa dystrophic epidermolysis bullosa pruriginosa

Similar variants

COL7A1 p.Pro1940Leu Conflicting classifications of pathogenicity ★ same residue
COL7A1 p.Pro1940fs Pathogenic ★ same residue
COL7A1 c.1240+1G>T Likely pathogenic ★★ same condition
COL7A1 c.1637-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.1906+1G>T Likely pathogenic ★★ same condition
COL7A1 c.2171-2A>G Likely pathogenic ★★ same condition
COL7A1 c.2587+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2587+40G>A Pathogenic/Likely 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-pro1940 (accessed [today's date]).

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