Is COL7A1 p.Pro1687Ser (c.5059C>T) pathogenic?

COL7A1 p.Pro1687Ser (c.5059C>T) is classified Uncertain significance in COL7A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.1008); Very rare (popmax 8.49e-05%, nfe); Associated with epidermolysis bullosa dystrophica.

What condition is associated with COL7A1 p.Pro1687Ser (c.5059C>T)?

COL7A1 p.Pro1687Ser (c.5059C>T) is associated with epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Pro1687Ser (c.5059C>T) in the general population?

COL7A1 p.Pro1687Ser (c.5059C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about COL7A1 p.Pro1687Ser (c.5059C>T)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro1687Ser

c.5059C>T · VCV4065199

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

epidermolysis bullosa dystrophica

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.648	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	24.7	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 8.49e-05% European (non-Finnish) · 1/1,177,962 alleles

Overall 0.000137% 2/1,457,538 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,296
European (non-Finnish)grpmax	8.49e-05%	1,177,962

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.Pro1687Ser
Coding: c.5059C>T
MANE Select: NM_000094
Type: single nucleotide variant
Location: chr3:48580338 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 1687: the 'disordered' region; the 'triple-helical region' region

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

Disease context

epidermolysis bullosa dystrophica — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL7A1 p.Pro1687= Likely benign ★ 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
COL7A1 c.2993-2A>G 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-pro1687ser (accessed [today's date]).

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