Is KRT83 p.Glu352= (c.1056A>G) pathogenic?

KRT83 p.Glu352= (c.1056A>G) is classified Benign in KRT83 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 48.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with monilethrix.

What condition is associated with KRT83 p.Glu352= (c.1056A>G)?

KRT83 p.Glu352= (c.1056A>G) 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.Glu352=

Q: How common is KRT83 p.Glu352= (c.1056A>G) in the general population?

KRT83 p.Glu352= (c.1056A>G) is common (popmax 48.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1056A>G · rs2248473 · VCV309504

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 48.6%, 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 0.11	GERP -0.24, phastCons 0.014
Overall
CADD	7.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.6% African / African-American · 36,349/74,752 alleles

Filtering AF 48.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 48%

Overall 40.9% 659,181/1,611,294 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	59.4%	2
African / African-Americangrpmax	48.6%	2
South Asian	42.7%	2
European (non-Finnish)	42.2%	2
Remaining individualsnot grpmax-eligible	40.4%	2
Middle Eastern	37.7%	3
Finnishnot grpmax-eligible	35.2%	3
Ashkenazi Jewishnot grpmax-eligible	34.8%	3
Admixed American	28.9%	3
East Asian	20.8%	5

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu352=
Coding: c.1056A>G
MANE Select: NM_002282
dbSNP: rs2248473
Type: single nucleotide variant
Location: chr12:52316099 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 352: 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-glu352 (accessed [today's date]).

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