Is KRT2 p.Ile182= (c.546C>A) pathogenic?

KRT2 p.Ile182= (c.546C>A) is classified Likely benign in KRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00932%, nfe); Associated with superficial epidermolytic ichthyosis.

What condition is associated with KRT2 p.Ile182= (c.546C>A)?

KRT2 p.Ile182= (c.546C>A) is associated with superficial epidermolytic ichthyosis (ClinVar).

How common is KRT2 p.Ile182= (c.546C>A) in the general population?

KRT2 p.Ile182= (c.546C>A) is very rare (popmax 0.00932%, nfe) (gnomAD).

How is Superficial epidermolytic ichthyosis inherited?

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

KRT2 p.Ile182=

c.546C>A · rs371939083 · VCV883366

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

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 3.5	GERP 2.1, phastCons 1
Overall
CADD	8.665	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00932% European (non-Finnish) · 110/1,180,028 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.007% 113/1,614,024 alleles · very rare exomes 105/1,461,870 · genomes 8/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00932%	10,728
African / African-American	0.00401%	24,969

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.Ile182=
Coding: c.546C>A
MANE Select: NM_000423
dbSNP: rs371939083
Type: single nucleotide variant
Location: chr12:52651597 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.38
Residue 182: the if rod domain; a UniProt-annotated variant site (in ibs); the 'coil 1a' 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-ile182 (accessed [today's date]).

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