CAST p.Gln56=

Q: Is CAST p.Gln56= (c.168A>G) pathogenic?

CAST p.Gln56= (c.168A>G) is classified Benign in CAST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 25.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome.

Q: What condition is associated with CAST p.Gln56= (c.168A>G)?

CAST p.Gln56= (c.168A>G) is associated with peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (ClinVar).

Q: How common is CAST p.Gln56= (c.168A>G) in the general population?

CAST p.Gln56= (c.168A>G) is common (popmax 25.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Peeling skin-leukonychia-acral punctate keratoses-cheilitis-knuckle pads syndrome inherited?

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

c.168A>G · rs9667 · VCV1192696

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 25.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.022	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.9
Overall
CADD	1.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.8% East Asian · 11,542/44,754 alleles

Filtering AF 25.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.2%

Overall 20.3% 326,674/1,608,786 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	25.8%	4
Finnishnot grpmax-eligible	25.5%	4
Admixed American	22.6%	4
South Asian	22.1%	5
European (non-Finnish)	20.3%	5
Remaining individualsnot grpmax-eligible	19.6%	5
Middle Eastern	15.5%	6
Ashkenazi Jewishnot grpmax-eligible	13.4%	7
African / African-American	12.8%	8
Amishnot grpmax-eligible	8.66%	12

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: CAST
Protein: p.Gln56=
Coding: c.168A>G
dbSNP: rs9667
Type: single nucleotide variant
Location: chr5:96695865 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.67
Residue 56: the 'disordered' region

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

Disease context

peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Peeling skin-leukonychia-acral punctate keratoses-cheilitis-knuckle pads syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CAST c.1525-106G>A Benign ★★ same condition
CAST p.Ala403Pro Benign ★★ ⚠ same condition
CAST p.Ala481Thr Benign ★★ same condition
CAST p.Cys491Ser Benign ★★ same condition
CAST c.630+1G>T Likely pathogenic ★ same condition
CAST c.630+2T>C Likely pathogenic ★ same condition
CAST p.Gln628Ter Likely pathogenic ★ same condition
CAST p.Gln97Ter Likely pathogenic ★ 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/cast-p-gln56 (accessed [today's date]).

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