Is KRT5 p.Ser5Ter (c.14C>A) pathogenic?

KRT5 p.Ser5Ter (c.14C>A) is classified Pathogenic in KRT5 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2006-03-01). No allele count reported in gnomAD v4.1 (AN 1,613,342); Associated with Dowling-Degos disease 1.

What condition is associated with KRT5 p.Ser5Ter (c.14C>A)?

KRT5 p.Ser5Ter (c.14C>A) is associated with Dowling-Degos disease 1 (ClinVar).

How common is KRT5 p.Ser5Ter (c.14C>A) in the general population?

KRT5 p.Ser5Ter (c.14C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,342) (gnomAD).

How is Dowling-Degos disease inherited?

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

KRT5 p.Ser5Ter

c.14C>A · rs58751565 · VCV14647

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,342)

Conditions

Dowling-Degos disease 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,342). 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: KRT5
Protein: p.Ser5Ter
Coding: c.14C>A
MANE Select: NM_000424
dbSNP: rs58751565
Type: single nucleotide variant
Location: chr12:52520283 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 5: a modified residue (phosphoserine); the 'head' region; a UniProt-annotated variant site (in ddd1); the 'disordered' region

Full KRT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Dowling-Degos disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dowling-Degos disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

KRT5 p.Arg331Cys Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Lys199Asn Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Met327Thr Pathogenic ★★ same condition
KRT5 p.Pro217Leu Uncertain significance ★★ same condition
KRT5 p.Ser75Tyr Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg37Gln Benign/Likely benign ★★ ⚠ same condition
KRT5 p.Thr198= Benign ★★ same condition
KRT5 p.Arg352Cys 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/krt5-p-ser5ter (accessed [today's date]).

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