Is KRT14 p.Ile400Ser (c.1199T>G) pathogenic?

KRT14 p.Ile400Ser (c.1199T>G) is classified Uncertain significance in KRT14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-28). AlphaMissense: likely pathogenic (0.6663); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT14 p.Ile400Ser (c.1199T>G)?

KRT14 p.Ile400Ser (c.1199T>G) is associated with Inborn genetic diseases (ClinVar).

How common is KRT14 p.Ile400Ser (c.1199T>G) in the general population?

KRT14 p.Ile400Ser (c.1199T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about KRT14 p.Ile400Ser (c.1199T>G)?

AlphaMissense predicts likely pathogenic (score 0.6663) — an in-silico prediction, not a clinical call.

KRT14 p.Ile400Ser

c.1199T>G · rs1352692209 · VCV2222076

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6663	likely pathogenic
REVEL	0.689	pathogenic-leaning
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 4,396 bp · p 3e-05 · regional, not allelic
Overall
CADD	24.9	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 0.000424% European (non-Finnish) · 5/1,179,986 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,492 alleles · very rare exomes 4/1,461,472 · genomes 1/152,020 · joint denominator

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: KRT14
Protein: p.Ile400Ser
Coding: c.1199T>G
MANE Select: NM_000526
dbSNP: rs1352692209
Type: single nucleotide variant
Location: chr17:41583310 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.00 · 6 PDB
Residue 400: the if rod domain; the 'coil 2' region; an α-helix

Full KRT14 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

KRT14 p.Arg407Trp Uncertain significance ★★ ⚠ same condition
KRT14 p.Arg41His Uncertain significance ★★ ⚠ same condition
KRT14 p.Arg449His Uncertain significance ★★ ⚠ same condition
KRT14 p.Arg469His Uncertain significance ★★ ⚠ same condition
KRT14 p.Gly27Ala Uncertain significance ★★ ⚠ same condition
KRT14 p.Gly47Arg Uncertain significance ★★ ⚠ same condition
KRT14 p.Ser435Leu Uncertain significance ★★ ⚠ same condition
KRT14 p.Trp150Arg 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/krt14-p-ile400ser (accessed [today's date]).

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