Is KRT9 p.Phe6Leu (c.16T>C) pathogenic?

KRT9 p.Phe6Leu (c.16T>C) is classified Uncertain significance in KRT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely pathogenic (0.6903); Ultra-rare (popmax 0.0174%, afr); Associated with Inborn genetic diseases.

What condition is associated with KRT9 p.Phe6Leu (c.16T>C)?

KRT9 p.Phe6Leu (c.16T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT9 p.Phe6Leu (c.16T>C) in the general population?

KRT9 p.Phe6Leu (c.16T>C) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about KRT9 p.Phe6Leu (c.16T>C)?

AlphaMissense predicts likely pathogenic (score 0.6903) — an in-silico prediction, not a clinical call.

KRT9 p.Phe6Leu

c.16T>C · rs200697505 · VCV3116796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6903 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6903	likely pathogenic
REVEL	0.19	benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.61	GERP -3, phastCons 0.013
Regional constraint	o/e 1.15	unconstrained · MANE · 473 bp · p 0.034 · regional, not allelic
Overall
CADD	17.0	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

Grpmax group 0.0174% African / African-American · 13/74,646 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00815%

Overall 0.000947% 15/1,583,888 alleles · ultra-rare exomes 5/1,431,642 · genomes 10/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,742
Admixed American	0.00178%	56,256
Remaining individualsnot grpmax-eligible	0.00163%	61,332

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.Phe6Leu
Coding: c.16T>C
MANE Select: NM_000226
dbSNP: rs200697505
Type: single nucleotide variant
Location: chr17:41571977 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.43
Residue 6: the 'head' region; the 'disordered' 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.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
KRT9 p.Ser357Pro Uncertain significance ★★ ⚠ same condition
KRT9 p.Ser8Leu 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-phe6leu (accessed [today's date]).

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