Is KRT14 p.Ser321fs (c.962_970delinsCCAACACCGCTCT) pathogenic?

KRT14 p.Ser321fs (c.962970delinsCCAACACCGCTCT) is classified Pathogenic in KRT14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). Associated with epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive.

What condition is associated with KRT14 p.Ser321fs (c.962_970delinsCCAACACCGCTCT)?

KRT14 p.Ser321fs (c.962_970delinsCCAACACCGCTCT) is associated with epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive (ClinVar).

KRT14 p.Ser321fs

Q: How is Autosomal recessive generalized epidermolysis bullosa simplex inherited?

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

c.962_970delinsCCAACACCGCTCT · VCV4854025

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.35	GERP -3.4, phastCons 0.91
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.

Variant & gene context

Gene: KRT14
Protein: p.Ser321fs
Coding: c.962_970delinsCCAACACCGCTCT
MANE Select: NM_000526
Type: Indel
Location: chr17:41583634 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.00 · 6 PDB
Residue 321: the if rod domain; the 'coil 2' region

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

Disease context

epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive generalized epidermolysis bullosa simplex (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

KRT14 p.Ser321= Likely benign ★★ same residue
KRT14 c.526-2A>C Likely pathogenic ★★ same condition
KRT14 p.Arg388His Likely pathogenic ★★ same condition
KRT14 p.Glu256Ter Pathogenic ★★ same condition
KRT14 p.Ile31fs Pathogenic ★★ same condition
KRT14 p.Met272Thr Pathogenic ★★ same condition
KRT14 p.Trp305Ter Pathogenic ★★ same condition
KRT14 p.Gly47Arg Uncertain significance ★★ ⚠ 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-ser321fs (accessed [today's date]).

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