Is KRT5 p.Arg10Trp (c.28C>T) pathogenic?

KRT5 p.Arg10Trp (c.28C>T) is classified Uncertain significance in KRT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: ambiguous (0.4405); Ultra-rare (popmax 0.02%, afr); Associated with Inborn genetic diseases.

What condition is associated with KRT5 p.Arg10Trp (c.28C>T)?

KRT5 p.Arg10Trp (c.28C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT5 p.Arg10Trp (c.28C>T) in the general population?

KRT5 p.Arg10Trp (c.28C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about KRT5 p.Arg10Trp (c.28C>T)?

AlphaMissense predicts ambiguous (score 0.4405) — an in-silico prediction, not a clinical call.

KRT5 p.Arg10Trp

c.28C>T · VCV3536085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4405 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4405	ambiguous
REVEL	0.169	moderately benign-leaning
SaProt	LLR -14.83	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,321 bp · p 0.7 · regional, not allelic
Overall
CADD	25.2	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 0.02% African / African-American · 15/75,060 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.00607% 98/1,613,652 alleles · ultra-rare exomes 82/1,461,332 · genomes 16/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,004
Admixed American	0.00666%	15,004
European (non-Finnish)	0.00585%	17,102
Remaining individualsnot grpmax-eligible	0.0048%	20,831
East Asian	0.00446%	22,435
South Asian	0.00439%	22,763
Finnishnot grpmax-eligible	0.00157%	63,650

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.Arg10Trp
Coding: c.28C>T
MANE Select: NM_000424
Type: single nucleotide variant
Location: chr12:52520269 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 10: the 'head' region; a UniProt-annotated variant site (in ddd1); the 'disordered' region

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.Arg10= Benign/Likely benign ★★ same residue
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

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-arg10trp (accessed [today's date]).

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