Is DSP p.Arg27Gly (c.79C>G) pathogenic?

DSP p.Arg27Gly (c.79C>G) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.2471); Very rare (popmax 8.51e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Arg27Gly (c.79C>G)?

DSP p.Arg27Gly (c.79C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is DSP p.Arg27Gly (c.79C>G) in the general population?

DSP p.Arg27Gly (c.79C>G) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about DSP p.Arg27Gly (c.79C>G)?

AlphaMissense predicts likely benign (score 0.2471) — an in-silico prediction, not a clinical call.

DSP p.Arg27Gly

c.79C>G · rs762198350 · VCV3224251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2471 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2471	likely benign
REVEL	0.353	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	24.8	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 8.51e-05% European (non-Finnish) · 1/1,174,528 alleles

Overall 6.91e-05% 1/1,447,722 alleles · very rare

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.Arg27Gly
Coding: c.79C>G
MANE Select: NM_004415
dbSNP: rs762198350
Type: single nucleotide variant
Location: chr6:7541994 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 27: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSP p.Arg27His Uncertain significance ★★ same residue
DSP p.Arg27= Likely benign ★★ same residue
DSP c.778-2A>G Likely pathogenic ★★ same condition
DSP p.Arg1267Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg160Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1738Ter Pathogenic ★★ same condition
DSP p.Arg270Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg425Ter Pathogenic/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-arg27gly (accessed [today's date]).

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