Is COL7A1 p.Gly1326Val (c.3977G>T) pathogenic?

COL7A1 p.Gly1326Val (c.3977G>T) is classified Likely pathogenic in COL7A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-19). AlphaMissense: likely pathogenic (0.5829); Absent from gnomAD v4.1; Associated with recessive dystrophic epidermolysis bullosa.

What condition is associated with COL7A1 p.Gly1326Val (c.3977G>T)?

COL7A1 p.Gly1326Val (c.3977G>T) is associated with recessive dystrophic epidermolysis bullosa (ClinVar).

How common is COL7A1 p.Gly1326Val (c.3977G>T) in the general population?

COL7A1 p.Gly1326Val (c.3977G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL7A1 p.Gly1326Val (c.3977G>T)?

AlphaMissense predicts likely pathogenic (score 0.5829) — an in-silico prediction, not a clinical call.

COL7A1 p.Gly1326Val

Q: How is Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.3977G>T · VCV3393058

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5829 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

recessive dystrophic epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.5829	likely pathogenic ✓ concordant with ClinVar
REVEL	0.869	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	Δ0.20	acceptor gain, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	25.2	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

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.Gly1326Val
Coding: c.3977G>T
MANE Select: NM_000094
Type: single nucleotide variant
Location: chr3:48584944 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 1326: the 'disordered' region; the 'triple-helical region' region; the 'interrupted collagenous region' region

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

Disease context

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

For Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

COL7A1 p.Gly1326= Likely benign ★ 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.266+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.266+2T>C 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-gly1326val (accessed [today's date]).

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