Is KRT83 p.Ser28Ile (c.83G>T) pathogenic?

KRT83 p.Ser28Ile (c.83G>T) is classified Uncertain significance in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.2185); Very rare (popmax 8.48e-05%, nfe); Associated with monilethrix.

What condition is associated with KRT83 p.Ser28Ile (c.83G>T)?

KRT83 p.Ser28Ile (c.83G>T) is associated with monilethrix (ClinVar).

How common is KRT83 p.Ser28Ile (c.83G>T) in the general population?

KRT83 p.Ser28Ile (c.83G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Monilethrix inherited?

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

What do computational predictors say about KRT83 p.Ser28Ile (c.83G>T)?

AlphaMissense predicts likely benign (score 0.2185) — an in-silico prediction, not a clinical call.

KRT83 p.Ser28Ile

c.83G>T · rs886049622 · VCV309545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

monilethrix

Computational evidence

Protein change
AlphaMissense	0.2185	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.87, phastCons 0.66
Regional constraint	o/e 0.98	unconstrained · MANE · 6,701 bp · p 0.63 · regional, not allelic
Overall
CADD	17.26	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,936 alleles

Overall 6.2e-05% 1/1,613,458 alleles · very rare exomes 1/1,461,094 · genomes 0/152,364 · 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: KRT83
Protein: p.Ser28Ile
Coding: c.83G>T
MANE Select: NM_002282
dbSNP: rs886049622
Type: single nucleotide variant
Location: chr12:52321253 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 28: the 'head' 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.Ser28Gly Likely benign ★ same residue
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

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-ser28ile (accessed [today's date]).

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