Is KRT14 p.Arg416fs (c.1246del) pathogenic?

KRT14 p.Arg416fs (c.1246del) is classified Pathogenic in KRT14 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-11-11). No gnomAD frequency available for this variant; Associated with epidermolysis bullosa simplex 1A, generalized severe.

What condition is associated with KRT14 p.Arg416fs (c.1246del)?

KRT14 p.Arg416fs (c.1246del) is associated with epidermolysis bullosa simplex 1A, generalized severe (ClinVar).

How common is KRT14 p.Arg416fs (c.1246del) in the general population?

KRT14 p.Arg416fs (c.1246del) is no gnomAD frequency available for this variant (gnomAD).

KRT14 p.Arg416fs

Q: How is Autosomal dominant generalized epidermolysis bullosa simplex, severe form inherited?

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

c.1246del · rs58357841 · VCV66323

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

epidermolysis bullosa simplex 1A, generalized severe

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KRT14
Protein: p.Arg416fs
Coding: c.1246del
MANE Select: NM_000526
dbSNP: rs58357841
Type: Deletion
Location: chr17:41583263 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.00 · 6 PDB
Residue 416: the if rod domain; a UniProt-annotated variant site (in ebs1a); the 'coil 2' region; an α-helix

Full KRT14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa simplex 1A, generalized severe — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant generalized epidermolysis bullosa simplex, severe form (Orphanet):

Inheritance: Autosomal dominant
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

KRT14 p.Glu205fs Likely pathogenic ★ same condition
KRT14 p.Glu409fs Pathogenic ★ same condition
KRT14 p.Arg416Cys Uncertain significance ★ ⚠ same residue
KRT14 p.Arg416Ser Uncertain significance ★ ⚠ same residue
KRT14 p.Arg416= Likely benign ★ same residue
KRT14 p.Tyr415_Glu420del Pathogenic same condition
KRT14 c.526-2A>C Likely pathogenic ★★ same condition
KRT14 p.Arg125Cys 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/krt14-p-arg416fs (accessed [today's date]).

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