Is COL7A1 p.Pro657Ser (c.1969C>T) pathogenic?

COL7A1 p.Pro657Ser (c.1969C>T) is classified Uncertain significance in COL7A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.2633); Absent from gnomAD v4.1; Associated with epidermolysis bullosa dystrophica.

What condition is associated with COL7A1 p.Pro657Ser (c.1969C>T)?

COL7A1 p.Pro657Ser (c.1969C>T) is associated with epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Pro657Ser (c.1969C>T) in the general population?

COL7A1 p.Pro657Ser (c.1969C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL7A1 p.Pro657Ser (c.1969C>T)?

AlphaMissense predicts likely benign (score 0.2633) — an in-silico prediction, not a clinical call.

COL7A1 p.Pro657Ser

c.1969C>T · rs886058641 · VCV345868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2633 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

epidermolysis bullosa dystrophica

Computational evidence

Protein change
AlphaMissense	0.2633	likely benign
REVEL	0.328	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 6,279 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL7A1
Protein: p.Pro657Ser
Coding: c.1969C>T
MANE Select: NM_000094
dbSNP: rs886058641
Type: single nucleotide variant
Location: chr3:48590294 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 657: the 'nonhelical region (nc1)' region; the fibronectin type-iii 5 domain

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.Pro657Arg 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
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-pro657ser (accessed [today's date]).

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