Is KRT83 p.Asp444= (c.1332T>C) pathogenic?

KRT83 p.Asp444= (c.1332T>C) is classified Benign in KRT83 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 85.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with monilethrix.

What condition is associated with KRT83 p.Asp444= (c.1332T>C)?

KRT83 p.Asp444= (c.1332T>C) is associated with monilethrix (ClinVar).

How is Monilethrix inherited?

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

KRT83 p.Asp444=

Q: How common is KRT83 p.Asp444= (c.1332T>C) in the general population?

KRT83 p.Asp444= (c.1332T>C) is common (popmax 85.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1332T>C · rs2857670 · VCV309499

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 85.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

monilethrix

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -3.7, phastCons 0.99
Overall
CADD	6.755	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 85.5% African / African-American · 64,025/74,890 alleles

Filtering AF 84.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 84.7%

Overall 66.9% 1,073,519/1,604,820 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	85.5%	1
Amishnot grpmax-eligible	77.1%	1
Remaining individualsnot grpmax-eligible	67.4%	1
Middle Eastern	67.1%	1
South Asian	66.8%	1
East Asian	66.7%	1
European (non-Finnish)	66.3%	2
Finnishnot grpmax-eligible	65.7%	2
Ashkenazi Jewishnot grpmax-eligible	62.2%	2
Admixed American	58.7%	2

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: KRT83
Protein: p.Asp444=
Coding: c.1332T>C
MANE Select: NM_002282
dbSNP: rs2857670
Type: single nucleotide variant
Location: chr12:52314781 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 444: the 'tail' region

Full KRT83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

monilethrix — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Monilethrix (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

KRT83 p.Glu407Lys Likely pathogenic ★★ same condition
KRT83 p.Arg168Trp Uncertain significance ★★ ⚠ same condition
KRT83 p.Arg272Gln Uncertain significance ★★ ⚠ same condition
KRT83 p.Glu172Lys Uncertain significance ★★ ⚠ same condition
KRT83 c.1041+6A>G Benign ★★ same condition
KRT83 c.1042-4C>A Benign ★★ same condition
KRT83 c.750+15A>G Benign ★★ same condition
KRT83 c.*138C>T Benign ★★ 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/krt83-p-asp444 (accessed [today's date]).

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