Is KRT83 p.Ser487Phe (c.1460C>T) pathogenic?

KRT83 p.Ser487Phe (c.1460C>T) is classified Uncertain significance in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: likely benign (0.0728); Very rare (popmax 0.00555%, amr).

How common is KRT83 p.Ser487Phe (c.1460C>T) in the general population?

KRT83 p.Ser487Phe (c.1460C>T) is very rare (popmax 0.00555%, amr) (gnomAD).

What do computational predictors say about KRT83 p.Ser487Phe (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

KRT83 p.Ser487Phe

c.1460C>T · rs765607233 · VCV2398922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00555%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP -1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,701 bp · p 0.63 · regional, not allelic
Overall
CADD	17.08	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 0.00555% Admixed American · 3/54,100 alleles

Filtering AF 0.00147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.00178% 28/1,573,128 alleles · very rare exomes 24/1,420,952 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00555%	18,033
African / African-American	0.0027%	37,105
European (non-Finnish)	0.0019%	52,700
Remaining individualsnot grpmax-eligible	0.00164%	60,828

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.Ser487Phe
Coding: c.1460C>T
MANE Select: NM_002282
dbSNP: rs765607233
Type: single nucleotide variant
Location: chr12:52314653 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 487: the 'tail' 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-ser487phe (accessed [today's date]).

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