Is KRT83 p.Ser54Arg (c.162C>A) pathogenic?

KRT83 p.Ser54Arg (c.162C>A) is classified Uncertain significance in KRT83 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.6584); Very rare (popmax 0.00223%, eas).

How common is KRT83 p.Ser54Arg (c.162C>A) in the general population?

KRT83 p.Ser54Arg (c.162C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about KRT83 p.Ser54Arg (c.162C>A)?

AlphaMissense predicts likely pathogenic (score 0.6584) — an in-silico prediction, not a clinical call.

KRT83 p.Ser54Arg

c.162C>A · VCV4095258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6584	likely pathogenic
REVEL	0.323	indeterminate
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -0.35
Regional constraint	o/e 0.98	unconstrained · MANE · 6,701 bp · p 0.63 · regional, not allelic
Overall
CADD	15.94	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,612,592 alleles · very rare exomes 4/1,460,344 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	0.000339%	294,849

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.Ser54Arg
Coding: c.162C>A
MANE Select: NM_002282
Type: single nucleotide variant
Location: chr12:52321174 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81
Residue 54: the 'head' region

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

Similar variants

KRT83 p.Ser54Thr 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
KRT83 p.Arg321Cys 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-ser54arg (accessed [today's date]).

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