Is KRT83 p.Arg315= (c.945G>A) pathogenic?

KRT83 p.Arg315= (c.945G>A) is classified Benign in KRT83 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-18). Rare (popmax 0.885%, eas); Associated with monilethrix.

What condition is associated with KRT83 p.Arg315= (c.945G>A)?

KRT83 p.Arg315= (c.945G>A) is associated with monilethrix (ClinVar).

How common is KRT83 p.Arg315= (c.945G>A) in the general population?

KRT83 p.Arg315= (c.945G>A) is rare (popmax 0.885%, eas) (gnomAD).

How is Monilethrix inherited?

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

KRT83 p.Arg315=

c.945G>A · rs138807826 · VCV883999

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.885%, eas)

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 -7.4	GERP -3.1
Overall
CADD	5.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.885% East Asian · 397/44,864 alleles

Filtering AF 0.813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.785%

Overall 0.0247% 399/1,614,120 alleles · rare exomes 381/1,461,892 · genomes 18/152,228 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.885%	113
Remaining individualsnot grpmax-eligible	0.0032%	31,251

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.Arg315=
Coding: c.945G>A
MANE Select: NM_002282
dbSNP: rs138807826
Type: single nucleotide variant
Location: chr12:52316564 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 315: 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-arg315 (accessed [today's date]).

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