Is DES p.Ser31Arg (c.93T>G) pathogenic?

DES p.Ser31Arg (c.93T>G) is classified Uncertain significance in DES (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-12). AlphaMissense: ambiguous (0.5013); Ultra-rare (popmax 0.0101%, amr); Associated with dilated cardiomyopathy 1I.

What condition is associated with DES p.Ser31Arg (c.93T>G)?

DES p.Ser31Arg (c.93T>G) is associated with dilated cardiomyopathy 1I, neurogenic scapuloperoneal syndrome, Kaeser type, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Ser31Arg (c.93T>G) in the general population?

DES p.Ser31Arg (c.93T>G) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

What do computational predictors say about DES p.Ser31Arg (c.93T>G)?

AlphaMissense predicts ambiguous (score 0.5013) — an in-silico prediction, not a clinical call.

DES p.Ser31Arg

c.93T>G · rs2017800 · VCV582559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.5013 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Conditions

dilated cardiomyopathy 1I

Computational evidence

Protein change
AlphaMissense	0.5013	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -8.21	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -3.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	21.1	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 0.0101% Admixed American · 6/59,152 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00299%

Overall 0.00349% 56/1,604,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,859
European (non-Finnish)	0.00416%	24,015
Remaining individualsnot grpmax-eligible	0.00161%	61,944

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: DES
Protein: p.Ser31Arg
Coding: c.93T>G
MANE Select: NM_001927
dbSNP: rs2017800
Type: single nucleotide variant
Location: chr2:219418555 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 31: a modified residue (phosphoserine); the 'head' region

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

Disease context

dilated cardiomyopathy 1I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurogenic scapuloperoneal syndrome, Kaeser type myofibrillar myopathy 1

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

DES p.Ser31Cys Uncertain significance ★★ ⚠ same residue
DES p.Ser31= Benign ★ same residue
DES c.1289-2A>G Pathogenic/Likely pathogenic ★★ same condition
DES c.579-2A>C Likely pathogenic ★★ same condition
DES c.735+1G>A Pathogenic/Likely pathogenic ★★ same condition
DES c.735+1G>C Pathogenic/Likely pathogenic ★★ same condition
DES c.735+3A>G Pathogenic ★★ same condition
DES p.Ala120Pro 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/des-p-ser31arg (accessed [today's date]).

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