Is KRT6C p.Ter565= (c.1694A>G) pathogenic?

KRT6C p.Ter565= (c.1694A>G) is classified Likely benign in KRT6C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-05). Ultra-rare (popmax 0.0367%, amr); Associated with KRT6C-related disorder.

What condition is associated with KRT6C p.Ter565= (c.1694A>G)?

KRT6C p.Ter565= (c.1694A>G) is associated with KRT6C-related disorder (ClinVar).

How common is KRT6C p.Ter565= (c.1694A>G) in the general population?

KRT6C p.Ter565= (c.1694A>G) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

KRT6C p.Ter565=

c.1694A>G · rs746995539 · VCV3053196

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Conditions

KRT6C-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -2.7
Overall
CADD	8.531	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0367% Admixed American · 22/60,012 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00297% 48/1,613,988 alleles · ultra-rare exomes 46/1,461,840 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,728
Middle Eastern	0.0329%	3,038
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00161%	62,106

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.Ter565=
Coding: c.1694A>G
MANE Select: NM_173086
dbSNP: rs746995539
Type: single nucleotide variant
Location: chr12:52469063 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.63

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

Disease context

KRT6C-related disorder

Similar variants

KRT6C c.541-6T>C Likely benign same condition
KRT6C p.Arg40Cys Likely benign ⚠ same condition
KRT6C p.Gly111Asp Benign same condition
KRT6C p.Gly504= Likely benign same condition
KRT6C p.Gly88Arg Benign ⚠ same condition
KRT6C p.Ser227Asn Benign same condition
KRT6C p.Glu472Lys Pathogenic/Likely pathogenic ★★ same type
KRT6C p.Arg260Cys 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-ter565 (accessed [today's date]).

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