Is KRT83 p.Pro80Arg (c.239C>G) pathogenic?

KRT83 p.Pro80Arg (c.239C>G) is classified Uncertain significance in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). AlphaMissense: likely benign (0.1228); Very rare (popmax 0.00263%, nfe).

How common is KRT83 p.Pro80Arg (c.239C>G) in the general population?

KRT83 p.Pro80Arg (c.239C>G) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about KRT83 p.Pro80Arg (c.239C>G)?

AlphaMissense predicts likely benign (score 0.1228) — an in-silico prediction, not a clinical call.

KRT83 p.Pro80Arg

c.239C>G · rs150875897 · VCV2985103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1228	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.9, phastCons 0.77
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

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 0.00263% European (non-Finnish) · 31/1,179,894 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00198% 32/1,612,198 alleles · very rare exomes 30/1,459,946 · genomes 2/152,252 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00263%	38,061
Remaining individualsnot grpmax-eligible	0.0016%	62,314

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.Pro80Arg
Coding: c.239C>G
MANE Select: NM_002282
dbSNP: rs150875897
Type: single nucleotide variant
Location: chr12:52321097 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 80: the 'head' region

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

Similar variants

KRT83 p.Pro80Leu Uncertain significance ★★ ⚠ same residue
KRT83 p.Pro80Ala Uncertain significance ★ ⚠ same residue
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

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-pro80arg (accessed [today's date]).

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