Is KRT2 p.Phe113= (c.339C>T) pathogenic?

KRT2 p.Phe113= (c.339C>T) is classified Benign in KRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0159%, eas); Associated with superficial epidermolytic ichthyosis.

What condition is associated with KRT2 p.Phe113= (c.339C>T)?

KRT2 p.Phe113= (c.339C>T) is associated with superficial epidermolytic ichthyosis (ClinVar).

How common is KRT2 p.Phe113= (c.339C>T) in the general population?

KRT2 p.Phe113= (c.339C>T) is ultra-rare (popmax 0.0159%, eas) (gnomAD).

How is Superficial epidermolytic ichthyosis inherited?

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

KRT2 p.Phe113=

c.339C>T · rs532474326 · VCV309621

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

Conditions

superficial epidermolytic ichthyosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.4	GERP -3.9
Overall
CADD	0.418	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% East Asian · 7/44,162 alleles

Filtering AF 0.00736% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00524%

Overall 0.00355% 57/1,605,634 alleles · ultra-rare exomes 50/1,453,846 · genomes 7/151,788 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,309
Remaining individualsnot grpmax-eligible	0.0129%	7,755
South Asian	0.0121%	8,243
African / African-American	0.00938%	10,661
Finnishnot grpmax-eligible	0.00472%	21,169
European (non-Finnish)	0.0017%	58,762
Admixed American	0.00169%	59,026

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: KRT2
Protein: p.Phe113=
Coding: c.339C>T
MANE Select: NM_000423
dbSNP: rs532474326
Type: single nucleotide variant
Location: chr12:52651804 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.38
Residue 113: the 'head' region

Full KRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

superficial epidermolytic ichthyosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Superficial epidermolytic ichthyosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KRT2 p.Glu487Lys Pathogenic ★★ same condition
KRT2 p.Glu488Lys Likely pathogenic ★★ same condition
KRT2 c.1249-4A>G Benign ★★ same condition
KRT2 c.1249-7G>T Benign ★★ same condition
KRT2 c.861+6C>G Benign/Likely benign ★★ same condition
KRT2 c.*215C>T Benign ★★ same condition
KRT2 c.*42T>C Benign ★★ same condition
KRT2 p.Ala427= Benign ★★ 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/krt2-p-phe113 (accessed [today's date]).

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