Is KRT83 p.Ile100= (c.300A>C) pathogenic?

KRT83 p.Ile100= (c.300A>C) is classified Likely benign in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Ultra-rare (popmax 0.0193%, mid).

How common is KRT83 p.Ile100= (c.300A>C) in the general population?

KRT83 p.Ile100= (c.300A>C) is ultra-rare (popmax 0.0193%, mid) (gnomAD).

KRT83 p.Ile100=

c.300A>C · rs549134397 · VCV2643014

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, mid)

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 -2.3	GERP 0.81
Overall
CADD	8.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% Middle Eastern · 1/5,176 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00911% 147/1,612,764 alleles · ultra-rare exomes 115/1,460,510 · genomes 32/152,254 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.86%	54
Middle Easterngrpmax	0.0193%	5,176
African / African-American	0.0134%	7,485
Remaining individualsnot grpmax-eligible	0.0112%	8,912
East Asian	0.0111%	8,977
European (non-Finnish)	0.00865%	11,567
South Asian	0.00439%	22,756
Admixed American	0.00167%	60,030

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.Ile100=
Coding: c.300A>C
MANE Select: NM_002282
dbSNP: rs549134397
Type: single nucleotide variant
Location: chr12:52321036 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 100: the 'head' region

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

Similar variants

KRT83 p.Glu407Lys Likely pathogenic ★★ same type
KRT83 p.Arg130Cys Uncertain significance ★★ ⚠ same type
KRT83 p.Arg168Trp Uncertain significance ★★ ⚠ same type
KRT83 p.Arg272Gln Uncertain significance ★★ ⚠ same type
KRT83 p.Arg272Trp Uncertain significance ★★ ⚠ same type
KRT83 p.Arg293His Uncertain significance ★★ ⚠ same type
KRT83 p.Arg321Cys Uncertain significance ★★ ⚠ same type
KRT83 p.Arg321His Uncertain significance ★★ ⚠ same type

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-ile100 (accessed [today's date]).

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