Is KRT83 p.Ala339= (c.1017C>T) pathogenic?

KRT83 p.Ala339= (c.1017C>T) is classified Benign/Likely benign in KRT83 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-08). Rare (popmax 0.743%, mid); Associated with monilethrix.

What condition is associated with KRT83 p.Ala339= (c.1017C>T)?

KRT83 p.Ala339= (c.1017C>T) is associated with monilethrix (ClinVar).

How common is KRT83 p.Ala339= (c.1017C>T) in the general population?

KRT83 p.Ala339= (c.1017C>T) is rare (popmax 0.743%, mid) (gnomAD).

How is Monilethrix inherited?

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

KRT83 p.Ala339=

c.1017C>T · rs143467763 · VCV309509

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.743%, mid)

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 -20	GERP -3.8
Overall
CADD	4.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.743% Middle Eastern · 45/6,060 alleles

Filtering AF 0.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.544%

Overall 0.0797% 1,286/1,614,098 alleles · rare exomes 1,196/1,461,876 · genomes 90/152,222 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.743%	135
South Asian	0.603%	166
Ashkenazi Jewishnot grpmax-eligible	0.351%	285
Remaining individualsnot grpmax-eligible	0.123%	812
Admixed American	0.0533%	1,876
European (non-Finnish)	0.0396%	2,527
African / African-American	0.0133%	7,501
East Asian	0.00223%	44,862
Finnishnot grpmax-eligible	0.00156%	64,040

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.Ala339=
Coding: c.1017C>T
MANE Select: NM_002282
dbSNP: rs143467763
Type: single nucleotide variant
Location: chr12:52316492 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 339: the if rod domain; the 'coil 2' 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-ala339 (accessed [today's date]).

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