Is KRT83 p.Cys30Arg (c.88T>C) pathogenic?

KRT83 p.Cys30Arg (c.88T>C) is classified Uncertain significance in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: ambiguous (0.4775); Very rare (popmax 0.00551%, nfe).

How common is KRT83 p.Cys30Arg (c.88T>C) in the general population?

KRT83 p.Cys30Arg (c.88T>C) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about KRT83 p.Cys30Arg (c.88T>C)?

AlphaMissense predicts ambiguous (score 0.4775) — an in-silico prediction, not a clinical call.

KRT83 p.Cys30Arg

c.88T>C · VCV3289568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4775	ambiguous
REVEL	0.466	indeterminate
SaProt	LLR -6.80	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.89, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,701 bp · p 0.63 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00551% European (non-Finnish) · 65/1,179,912 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00428% 69/1,613,452 alleles · very rare exomes 69/1,461,092 · genomes 0/152,360 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,152
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00133%	75,076

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.Cys30Arg
Coding: c.88T>C
MANE Select: NM_002282
Type: single nucleotide variant
Location: chr12:52321248 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 30: 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-cys30arg (accessed [today's date]).

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