Is KRT1 p.Ser599Pro (c.1795T>C) pathogenic?

KRT1 p.Ser599Pro (c.1795T>C) is classified Uncertain significance in KRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-21). AlphaMissense: likely benign (0.1421); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with KRT1 p.Ser599Pro (c.1795T>C)?

KRT1 p.Ser599Pro (c.1795T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT1 p.Ser599Pro (c.1795T>C) in the general population?

KRT1 p.Ser599Pro (c.1795T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KRT1 p.Ser599Pro (c.1795T>C)?

AlphaMissense predicts likely benign (score 0.1421) — an in-silico prediction, not a clinical call.

KRT1 p.Ser599Pro

c.1795T>C · VCV4859037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1421	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -11.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.003	GERP -0.73, phastCons 0.56
Regional constraint	o/e 0.96	unconstrained · MANE · 5,152 bp · p 0.25 · regional, not allelic
Overall
CADD	16.56	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 0.00167% Admixed American · 1/59,958 alleles

Overall 6.21e-05% 1/1,610,660 alleles · very rare exomes 1/1,458,602 · genomes 0/152,058 · 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: KRT1
Protein: p.Ser599Pro
Coding: c.1795T>C
MANE Select: NM_006121
Type: single nucleotide variant
Location: chr12:52675333 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 599: the 'tail' region; the 'disordered' region

Full KRT1 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

KRT1 p.Gln190Lys Uncertain significance ★★ ⚠ same condition
KRT1 p.Gln466Arg Uncertain significance ★★ ⚠ same condition
KRT1 p.Gly585Trp Uncertain significance ★★ same condition
KRT1 p.Val80Met Uncertain significance ★★ same condition
KRT1 p.Ala362Thr Uncertain significance ★ ⚠ same condition
KRT1 p.Ala459Val Uncertain significance ★ same condition
KRT1 p.Arg29His Uncertain significance ★ ⚠ same condition
KRT1 p.Arg37His 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/krt1-p-ser599pro (accessed [today's date]).

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