Is KRT9 p.Phe465= (c.1395T>C) pathogenic?

KRT9 p.Phe465= (c.1395T>C) is classified Likely benign in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with KRT9 p.Phe465= (c.1395T>C)?

KRT9 p.Phe465= (c.1395T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT9 p.Phe465= (c.1395T>C) in the general population?

KRT9 p.Phe465= (c.1395T>C) is very rare (popmax 0.00667%, amr) (gnomAD).

KRT9 p.Phe465=

c.1395T>C · VCV4095311

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -0.024, phastCons 0.17
Overall
CADD	5.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,002 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00031% 5/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: KRT9
Protein: p.Phe465=
Coding: c.1395T>C
MANE Select: NM_000226
Type: single nucleotide variant
Location: chr17:41567750 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 465: the if rod domain; the 'disordered' region; the 'tail' region

Full KRT9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT9 p.Phe465Leu Uncertain significance ★ ⚠ same residue
KRT9 p.Phe465Cys Conflicting classifications of pathogenicity ★ same residue
KRT9 p.Arg13His Uncertain significance ★★ ⚠ same condition
KRT9 p.Gly116Asp Uncertain significance ★★ ⚠ same condition
KRT9 p.Gly193Glu Uncertain significance ★★ ⚠ same condition
KRT9 p.Gly507Arg Uncertain significance ★★ same condition
KRT9 p.Gly507Val Uncertain significance ★★ ⚠ same condition
KRT9 p.Ile341Val 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/krt9-p-phe465 (accessed [today's date]).

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