Is KRT6B p.Pro128= (c.384T>C) pathogenic?

KRT6B p.Pro128= (c.384T>C) is classified Benign in KRT6B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-27). Common (popmax 5.34%, afr) — too common for a highly-penetrant pathogenic allele; Associated with KRT6B-related disorder.

What condition is associated with KRT6B p.Pro128= (c.384T>C)?

KRT6B p.Pro128= (c.384T>C) is associated with KRT6B-related disorder (ClinVar).

KRT6B p.Pro128=

Q: How common is KRT6B p.Pro128= (c.384T>C) in the general population?

KRT6B p.Pro128= (c.384T>C) is common (popmax 5.34%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.384T>C · VCV3352705

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.34%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

KRT6B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	4.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.34% African / African-American · 3,697/69,226 alleles

Filtering AF 5.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.14%

Overall 0.304% 4,887/1,605,502 alleles · common exomes 2,259/1,457,024 · genomes 2,628/148,478 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.34%	19
Admixed American	0.547%	183
Middle Eastern	0.441%	227
Remaining individualsnot grpmax-eligible	0.402%	249
Ashkenazi Jewishnot grpmax-eligible	0.326%	306
South Asian	0.128%	783
European (non-Finnish)	0.0307%	3,257
East Asian	0.0267%	3,739
Finnishnot grpmax-eligible	0.00625%	16,008

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: KRT6B
Protein: p.Pro128=
Coding: c.384T>C
MANE Select: NM_005555
Type: single nucleotide variant
Location: chr12:52451695 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.76
Residue 128: the 'head' region

Full KRT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KRT6B-related disorder

Similar variants

KRT6B p.Gly66= Likely benign same condition
KRT6B p.Gly88Arg Benign same condition
KRT6B p.Leu61= Likely benign same condition
KRT6B p.Pro154= Likely benign same condition
KRT6B p.Ser60= Likely benign same condition
KRT6B p.Ser67= Likely benign same condition
KRT6B p.Asn172del Pathogenic ★★ same condition
KRT6B p.Glu461Lys Pathogenic/Likely pathogenic ★★ 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/krt6b-p-pro128 (accessed [today's date]).

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