Is KRT83 p.Ser271fs (c.811del) pathogenic?

KRT83 p.Ser271fs (c.811del) is classified Conflicting classifications of pathogenicity in KRT83 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-09). Rare (popmax 0.162%, sas); Associated with erythrokeratodermia variabilis et progressiva 5.

What condition is associated with KRT83 p.Ser271fs (c.811del)?

KRT83 p.Ser271fs (c.811del) is associated with erythrokeratodermia variabilis et progressiva 5 (ClinVar).

How common is KRT83 p.Ser271fs (c.811del) in the general population?

KRT83 p.Ser271fs (c.811del) is rare (popmax 0.162%, sas) (gnomAD).

How is Erythrokeratodermia variabilis inherited?

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

KRT83 p.Ser271fs

c.811del · rs753293188 · VCV446111

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.162%, sas)

Conditions

erythrokeratodermia variabilis et progressiva 5

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 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.88	GERP -0.24, phastCons 1
Overall
CADD	33.0	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

Grpmax group 0.162% South Asian · 148/91,086 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.00954% 154/1,614,230 alleles · rare exomes 143/1,461,894 · genomes 11/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.162%	615
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0064%	15,627

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KRT83
Protein: p.Ser271fs
Coding: c.811del
MANE Select: NM_002282
dbSNP: rs753293188
Type: Deletion
Location: chr12:52316963 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 271: the if rod domain; the 'linker 12' region

Full KRT83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

erythrokeratodermia variabilis et progressiva 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Erythrokeratodermia variabilis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

KRT83 p.Pro25fs Conflicting classifications of pathogenicity ★ same condition
KRT83 p.Ser271Asn Uncertain significance ★ ⚠ same residue
KRT83 p.Thr454Met Uncertain significance ★★ ⚠ same condition
KRT83 p.Ile254Val Benign/Likely benign ★★ same condition
KRT83 p.Pro27fs Likely pathogenic ★ same condition
KRT83 p.Cys389Ter Uncertain significance ★ same condition
KRT83 p.His258fs Uncertain significance ★ same type
KRT83 p.Leu159fs Uncertain significance ★ same type

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/krt83-p-ser271fs (accessed [today's date]).

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