Is KRT6A p.Ala161= (c.483T>C) pathogenic?

KRT6A p.Ala161= (c.483T>C) is classified Benign in KRT6A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-08-19). Common (popmax 68.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with pachyonychia congenita 3.

What condition is associated with KRT6A p.Ala161= (c.483T>C)?

KRT6A p.Ala161= (c.483T>C) is associated with pachyonychia congenita 3 (ClinVar).

How is Pachyonychia congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

KRT6A p.Ala161=

Q: How common is KRT6A p.Ala161= (c.483T>C) in the general population?

KRT6A p.Ala161= (c.483T>C) is common (popmax 68.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.483T>C · rs711317 · VCV1233095

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 68.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

pachyonychia congenita 3

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 -20	GERP -3.8
Overall
CADD	0.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.1% East Asian · 30,532/44,844 alleles

Filtering AF 67.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.2%

Overall 55.5% 895,238/1,613,506 alleles · common exomes 823,447/1,461,604 · genomes 71,791/151,902 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	68.1%	1
Admixed American	61.6%	2
Ashkenazi Jewishnot grpmax-eligible	60.1%	2
Finnishnot grpmax-eligible	57.9%	2
European (non-Finnish)	57.8%	2
Middle Eastern	55%	2
Remaining individualsnot grpmax-eligible	54.1%	2
Amishnot grpmax-eligible	52.1%	2
South Asian	42.6%	2
African / African-American	18.9%	5

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: KRT6A
Protein: p.Ala161=
Coding: c.483T>C
MANE Select: NM_005554
dbSNP: rs711317
Type: single nucleotide variant
Location: chr12:52492706 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.16 · 1 PDB
Residue 161: the 'head' region

Full KRT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pachyonychia congenita 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pachyonychia congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

KRT6A c.1460-1G>C Pathogenic/Likely pathogenic ★★ same condition
KRT6A p.Asn171Lys Pathogenic ★★ same condition
KRT6A p.Asn171Ser Pathogenic ★★ same condition
KRT6A p.Glu163Lys Pathogenic ★★ same condition
KRT6A p.Glu472Lys Pathogenic/Likely pathogenic ★★ same condition
KRT6A p.Leu170Phe Pathogenic ★★ same condition
KRT6A p.Arg375His Uncertain significance ★★ ⚠ same condition
KRT6A p.Lys550Asn 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/krt6a-p-ala161 (accessed [today's date]).

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