Is KRT83 p.Ala460= (c.1380C>T) pathogenic?

KRT83 p.Ala460= (c.1380C>T) is classified Likely benign in KRT83 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-18). Rare (popmax 0.213%, afr); Associated with KRT83-related disorder.

What condition is associated with KRT83 p.Ala460= (c.1380C>T)?

KRT83 p.Ala460= (c.1380C>T) is associated with KRT83-related disorder (ClinVar).

How common is KRT83 p.Ala460= (c.1380C>T) in the general population?

KRT83 p.Ala460= (c.1380C>T) is rare (popmax 0.213%, afr) (gnomAD).

KRT83 p.Ala460=

c.1380C>T · rs145323146 · VCV3057875

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.213%, afr)

Conditions

KRT83-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.13	GERP 0.77, phastCons 0.83
Overall
CADD	6.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% African / African-American · 159/74,746 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.0124% 197/1,594,028 alleles · rare exomes 97/1,441,682 · genomes 100/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.213%	470
Admixed American	0.026%	3,840
Remaining individualsnot grpmax-eligible	0.0211%	4,745
European (non-Finnish)	0.000854%	117,080

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.Ala460=
Coding: c.1380C>T
MANE Select: NM_002282
dbSNP: rs145323146
Type: single nucleotide variant
Location: chr12:52314733 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 460: the 'tail' region

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

Disease context

KRT83-related disorder

Similar variants

KRT83 p.Ala460Pro Uncertain significance ★ ⚠ same residue
KRT83 c.385-9G>C Likely benign same condition
KRT83 p.Ala354Thr Benign same condition
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

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-ala460 (accessed [today's date]).

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