Is KRT6C p.Asp153= (c.459C>T) pathogenic?

KRT6C p.Asp153= (c.459C>T) is classified Likely benign in KRT6C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). Ultra-rare (popmax 0.0128%, amr).

How common is KRT6C p.Asp153= (c.459C>T) in the general population?

KRT6C p.Asp153= (c.459C>T) is ultra-rare (popmax 0.0128%, amr) (gnomAD).

KRT6C p.Asp153=

c.459C>T · rs527527882 · VCV2643023

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP 1.8, phastCons 1
Overall
CADD	3.818	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0128% Admixed American · 7/54,638 alleles

Filtering AF 0.00601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00421%

Overall 0.00489% 69/1,412,434 alleles · ultra-rare exomes 68/1,281,720 · genomes 1/130,714 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.022%	4,538
Admixed Americangrpmax	0.0128%	7,805
East Asian	0.00985%	10,150
Remaining individualsnot grpmax-eligible	0.00532%	18,799
European (non-Finnish)	0.00386%	25,880
Ashkenazi Jewishnot grpmax-eligible	0.00369%	27,078
South Asian	0.00229%	43,582

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KRT6C
Protein: p.Asp153=
Coding: c.459C>T
MANE Select: NM_173086
dbSNP: rs527527882
Type: single nucleotide variant
Location: chr12:52473279 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.63
Residue 153: the 'head' region

Full KRT6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT6C p.Glu472Lys Pathogenic/Likely pathogenic ★★ same type
KRT6C p.Arg260Cys Uncertain significance ★★ ⚠ same type
KRT6C p.Arg349Trp Uncertain significance ★★ ⚠ same type
KRT6C p.Arg466Cys Uncertain significance ★★ ⚠ same type
KRT6C p.Asp331His Uncertain significance ★★ ⚠ same type
KRT6C p.Glu479Lys Uncertain significance ★★ same type
KRT6C p.Gly504Ser Uncertain significance ★★ ⚠ same type
KRT6C p.Gly525Ser 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/krt6c-p-asp153 (accessed [today's date]).

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