Is KRT1 p.Ile479Phe (c.1435A>T) pathogenic?

KRT1 p.Ile479Phe (c.1435A>T) is classified Pathogenic in KRT1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 1999-03-01). AlphaMissense: likely pathogenic (0.9836); Absent from gnomAD v4.1; Associated with ichthyosis, annular epidermolytic, 2.

What condition is associated with KRT1 p.Ile479Phe (c.1435A>T)?

KRT1 p.Ile479Phe (c.1435A>T) is associated with ichthyosis, annular epidermolytic, 2 (ClinVar).

How common is KRT1 p.Ile479Phe (c.1435A>T) in the general population?

KRT1 p.Ile479Phe (c.1435A>T) is absent from gnomAD v4.1 (gnomAD).

How is Annular epidermolytic ichthyosis inherited?

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

What do computational predictors say about KRT1 p.Ile479Phe (c.1435A>T)?

AlphaMissense predicts likely pathogenic (score 0.9836) — an in-silico prediction, not a clinical call.

KRT1 p.Ile479Phe

c.1435A>T · rs61218439 · VCV15912

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ichthyosis, annular epidermolytic, 2

Computational evidence

Protein change
AlphaMissense	0.9836	likely pathogenic ✓ concordant with ClinVar · top 7% in KRT1
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -13.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,152 bp · p 0.25 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KRT1
Protein: p.Ile479Phe
Coding: c.1435A>T
MANE Select: NM_006121
dbSNP: rs61218439
Type: single nucleotide variant
Location: chr12:52676315 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 479: the if rod domain; a UniProt-annotated variant site (in aei2); a UniProt-annotated variant site (in aei2 and ehk1); an α-helix; the 'coil 2' region

Full KRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ichthyosis, annular epidermolytic, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Annular epidermolytic ichthyosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KRT1 p.Ile479Thr Pathogenic/Likely pathogenic ★★ same residue
KRT1 p.Asn188Ser Pathogenic/Likely pathogenic ★★ same condition
KRT1 c.1255-1G>T Pathogenic ★★ same type
KRT1 c.591+1G>C Pathogenic ★★ same type
KRT1 p.Asn188Lys Pathogenic ★★ same type
KRT1 p.Ile195Asn Pathogenic/Likely pathogenic ★★ same type
KRT1 p.Leu187Phe Pathogenic ★★ same type
KRT1 p.Leu485Phe Pathogenic/Likely pathogenic ★★ 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/krt1-p-ile479phe (accessed [today's date]).

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