Is KRT83 p.Arg413Cys (c.1237C>T) pathogenic?

KRT83 p.Arg413Cys (c.1237C>T) is classified Uncertain significance in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-14). AlphaMissense: likely benign (0.1377); Very rare (popmax 0.005%, amr).

How common is KRT83 p.Arg413Cys (c.1237C>T) in the general population?

KRT83 p.Arg413Cys (c.1237C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about KRT83 p.Arg413Cys (c.1237C>T)?

AlphaMissense predicts likely benign (score 0.1377) — an in-silico prediction, not a clinical call.

KRT83 p.Arg413Cys

c.1237C>T · rs755560254 · VCV2249008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1377 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1377	likely benign
REVEL	0.735	pathogenic-leaning
SaProt	LLR -9.13	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.46	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.57	GERP 0.81
Regional constraint	o/e 0.98	unconstrained · MANE · 6,701 bp · p 0.63 · regional, not allelic
Overall
CADD	35.0	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 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00093% 15/1,612,512 alleles · very rare exomes 12/1,460,326 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.0016%	62,348
African / African-American	0.00134%	74,866
South Asian	0.0011%	91,014
European (non-Finnish)	0.000763%	131,099

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.Arg413Cys
Coding: c.1237C>T
MANE Select: NM_002282
dbSNP: rs755560254
Type: single nucleotide variant
Location: chr12:52315918 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 413: the if rod domain; the 'coil 2' 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-arg413cys (accessed [today's date]).

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