Is DES p.Arg164Ser (c.490C>A) pathogenic?

DES p.Arg164Ser (c.490C>A) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-16). AlphaMissense: ambiguous (0.4416); Very rare (popmax 0.00237%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg164Ser (c.490C>A)?

DES p.Arg164Ser (c.490C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Arg164Ser (c.490C>A) in the general population?

DES p.Arg164Ser (c.490C>A) is very rare (popmax 0.00237%, sas) (gnomAD).

What do computational predictors say about DES p.Arg164Ser (c.490C>A)?

AlphaMissense predicts ambiguous (score 0.4416) — an in-silico prediction, not a clinical call.

DES p.Arg164Ser

c.490C>A · rs2545248085 · VCV1744026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4416 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4416	ambiguous
REVEL	0.615	indeterminate
SaProt	LLR -8.75	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.72, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% South Asian · 2/84,506 alleles

Filtering AF 0.000393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000147%

Overall 0.000143% 2/1,403,364 alleles · very rare

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.Arg164Ser
Coding: c.490C>A
MANE Select: NM_001927
dbSNP: rs2545248085
Type: single nucleotide variant
Location: chr2:219418952 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 164: the if rod domain; the 'coil 1b' 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

Similar variants

DES p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
DES p.Arg454Trp Pathogenic/Likely pathogenic ★★ same condition
DES p.Glu401Asp Pathogenic/Likely pathogenic ★★ same condition
DES c.1245-3T>G Uncertain significance ★★ same condition
DES c.639+4A>G Uncertain significance ★★ same condition
DES p.Ala135Gly Uncertain significance ★★ ⚠ same condition
DES p.Ala137Val Uncertain significance ★★ ⚠ same condition
DES p.Ala213= Uncertain significance ★★ 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-arg164ser (accessed [today's date]).

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