Is DES p.Ala285Val (c.854C>T) pathogenic?

DES p.Ala285Val (c.854C>T) is classified Likely pathogenic in DES (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-30). AlphaMissense: likely pathogenic (0.9283); Very rare (popmax 0.00134%, afr); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Ala285Val (c.854C>T)?

DES p.Ala285Val (c.854C>T) is associated with myofibrillar myopathy 1, cardiomyopathy (ClinVar).

How common is DES p.Ala285Val (c.854C>T) in the general population?

DES p.Ala285Val (c.854C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Desminopathy 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.Ala285Val (c.854C>T)?

AlphaMissense predicts likely pathogenic (score 0.9283) — an in-silico prediction, not a clinical call.

DES p.Ala285Val

c.854C>T · rs1368507241 · VCV915758

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 1

Computational evidence

Protein change
AlphaMissense	0.9283	likely pathogenic ✓ concordant with ClinVar
REVEL	0.725	pathogenic-leaning
SaProt	LLR -10.84	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	29.6	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 0.00134% African / African-American · 1/74,844 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,880 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,844
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,012

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.Ala285Val
Coding: c.854C>T
MANE Select: NM_001927
dbSNP: rs1368507241
Type: single nucleotide variant
Location: chr2:219420613 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 285: the if rod domain; the 'interaction with neb' region; the 'coil 2a' region

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

Disease context

myofibrillar myopathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy

For Desminopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

DES p.Ala285Thr Uncertain significance ★★ ⚠ same residue
DES p.Ala285= Likely benign ★★ same residue
DES p.Ala285Gly 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
DES c.735+3A>G 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-ala285val (accessed [today's date]).

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