Is DSP p.Arg162Gly (c.484C>G) pathogenic?

DSP p.Arg162Gly (c.484C>G) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.7879); Very rare (popmax 0.00288%, nfe); Associated with keratosis palmoplantaris striata 2.

What condition is associated with DSP p.Arg162Gly (c.484C>G)?

DSP p.Arg162Gly (c.484C>G) is associated with keratosis palmoplantaris striata 2, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Arg162Gly (c.484C>G) in the general population?

DSP p.Arg162Gly (c.484C>G) is very rare (popmax 0.00288%, nfe) (gnomAD).

How is Striate palmoplantar keratoderma inherited?

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

What do computational predictors say about DSP p.Arg162Gly (c.484C>G)?

AlphaMissense predicts likely pathogenic (score 0.7879) — an in-silico prediction, not a clinical call.

DSP p.Arg162Gly

c.484C>G · rs760711308 · VCV546994

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Conditions

keratosis palmoplantaris striata 2

Computational evidence

Protein change
AlphaMissense	0.7879	likely pathogenic
REVEL	0.408	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,180,040 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00235% 38/1,613,844 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,228
European (non-Finnish)grpmax	0.00288%	34,707
Admixed American	0.00167%	59,996
African / African-American	0.00134%	74,884

Remaining individuals 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: DSP
Protein: p.Arg162Gly
Coding: c.484C>G
MANE Select: NM_004415
dbSNP: rs760711308
Type: single nucleotide variant
Location: chr6:7559287 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 162: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance)

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

Disease context

keratosis palmoplantaris striata 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8 lethal acantholytic epidermolysis bullosa cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis woolly hair-skin fragility syndrome

For Striate palmoplantar keratoderma (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

DSP p.Arg162Cys Conflicting classifications of pathogenicity ★ same residue
DSP p.Arg162His Conflicting classifications of pathogenicity ★ same residue
DSP p.Arg162Leu Conflicting classifications of pathogenicity ★ same residue
DSP c.1141-2A>T Likely pathogenic ★★ same condition
DSP c.1266+2T>C Likely pathogenic ★★ same condition
DSP c.1574+1G>A Likely pathogenic ★★ same condition
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.2297+1G>A 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/dsp-p-arg162gly (accessed [today's date]).

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