Is DES p.Arg383Ser (c.1147C>A) pathogenic?

DES p.Arg383Ser (c.1147C>A) is classified Uncertain significance in DES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-05). AlphaMissense: likely pathogenic (0.7624); Absent from gnomAD v4.1; Associated with DES-related disorder.

What condition is associated with DES p.Arg383Ser (c.1147C>A)?

DES p.Arg383Ser (c.1147C>A) is associated with DES-related disorder, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg383Ser (c.1147C>A) in the general population?

DES p.Arg383Ser (c.1147C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DES p.Arg383Ser (c.1147C>A)?

AlphaMissense predicts likely pathogenic (score 0.7624) — an in-silico prediction, not a clinical call.

DES p.Arg383Ser

c.1147C>A · rs748945548 · VCV1479493

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7624 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DES-related disorder

Computational evidence

Protein change
AlphaMissense	0.7624	likely pathogenic
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -10.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.71, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DES
Protein: p.Arg383Ser
Coding: c.1147C>A
MANE Select: NM_001927
dbSNP: rs748945548
Type: single nucleotide variant
Location: chr2:219421463 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 383: the 'coil 2b' region; the if rod domain; the 'interaction with neb' region

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

Disease context

DES-related disorder

Also linked: myofibrillar myopathy 1

Similar variants

DES p.Arg383Cys Uncertain significance ★★ ⚠ same residue
DES p.Arg383His Conflicting classifications of pathogenicity ★ ⚠ same residue
DES p.Arg383Pro Uncertain significance ★ ⚠ same residue
DES p.Arg383Leu Uncertain significance ★ ⚠ 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-arg383ser (accessed [today's date]).

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