Is DES p.Arg52Ser (c.154C>A) pathogenic?

DES p.Arg52Ser (c.154C>A) is classified Conflicting classifications of pathogenicity in DES (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.7661); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg52Ser (c.154C>A)?

DES p.Arg52Ser (c.154C>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg52Ser (c.154C>A) in the general population?

DES p.Arg52Ser (c.154C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DES p.Arg52Ser (c.154C>A)?

AlphaMissense predicts likely pathogenic (score 0.7661) — an in-silico prediction, not a clinical call.

DES p.Arg52Ser

c.154C>A · rs794728990 · VCV201712

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7661 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,122)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7661	likely pathogenic
REVEL	0.448	indeterminate
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.57, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	23.7	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

No allele count reported in gnomAD v4.1 (AN 1,603,122). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DES
Protein: p.Arg52Ser
Coding: c.154C>A
MANE Select: NM_001927
dbSNP: rs794728990
Type: single nucleotide variant
Location: chr2:219418616 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 52: the 'head' region

Full DES 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

Also linked: myofibrillar myopathy 1

Similar variants

DES p.Arg52His Uncertain significance ★ ⚠ same residue
DES p.Arg52Pro Uncertain significance ★ ⚠ same residue
DES p.Arg52= Likely benign ★ same residue
DES p.Arg52fs Pathogenic ★ 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

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-arg52ser (accessed [today's date]).

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