Is DES p.Gln172Pro (c.515A>C) pathogenic?

DES p.Gln172Pro (c.515A>C) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-18). AlphaMissense: likely pathogenic (0.9201); Absent from gnomAD v4.1; Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Gln172Pro (c.515A>C)?

DES p.Gln172Pro (c.515A>C) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Gln172Pro (c.515A>C) in the general population?

DES p.Gln172Pro (c.515A>C) is absent from gnomAD v4.1 (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.Gln172Pro (c.515A>C)?

AlphaMissense predicts likely pathogenic (score 0.9201) — an in-silico prediction, not a clinical call.

DES p.Gln172Pro

c.515A>C · rs2125166557 · VCV1361684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9201 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 1

Computational evidence

Protein change
AlphaMissense	0.9201	likely pathogenic
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -12.35	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	33.0	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.Gln172Pro
Coding: c.515A>C
MANE Select: NM_001927
dbSNP: rs2125166557
Type: single nucleotide variant
Location: chr2:219418977 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 172: the if rod domain; the 'coil 1b' 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

For Desminopathy (Orphanet):

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

Similar variants

DES p.Gln172Ter Pathogenic/Likely pathogenic ★★ same residue
DES p.Gln172= Conflicting classifications of pathogenicity ★ same residue
DES p.Gln172Leu 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-gln172pro (accessed [today's date]).

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