Is KRT5 p.Arg63Trp (c.187C>T) pathogenic?

KRT5 p.Arg63Trp (c.187C>T) is classified Conflicting classifications of pathogenicity in KRT5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-10-12). AlphaMissense: likely pathogenic (0.617); Ultra-rare (popmax 0.0285%, sas); Associated with Inborn genetic diseases.

What condition is associated with KRT5 p.Arg63Trp (c.187C>T)?

KRT5 p.Arg63Trp (c.187C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT5 p.Arg63Trp (c.187C>T) in the general population?

KRT5 p.Arg63Trp (c.187C>T) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

What do computational predictors say about KRT5 p.Arg63Trp (c.187C>T)?

AlphaMissense predicts likely pathogenic (score 0.617) — an in-silico prediction, not a clinical call.

KRT5 p.Arg63Trp

c.187C>T · rs776667863 · VCV792384

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.617 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.617	likely pathogenic
REVEL	0.509	indeterminate
SaProt	LLR -14.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,321 bp · p 0.7 · regional, not allelic
Overall
CADD	24.5	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 0.0285% South Asian · 26/91,078 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00291% 47/1,613,768 alleles · ultra-rare exomes 46/1,461,666 · genomes 1/152,102 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
Admixed American	0.01%	10,000
East Asian	0.00445%	22,448
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.00102%	98,325

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: KRT5
Protein: p.Arg63Trp
Coding: c.187C>T
MANE Select: NM_000424
dbSNP: rs776667863
Type: single nucleotide variant
Location: chr12:52520110 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 63: the 'head' region; a UniProt-annotated variant site (in ddd1)

Full KRT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT5 p.Pro25Leu Pathogenic ★★ same condition
KRT5 p.Ala101Thr Uncertain significance ★★ ⚠ same condition
KRT5 p.Ala20Thr Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg169His Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg239Cys Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg354Trp Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg559Gln Uncertain significance ★★ ⚠ same condition
KRT5 p.Arg585Trp Uncertain significance ★★ ⚠ same condition

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/krt5-p-arg63trp (accessed [today's date]).

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