Is DES p.Pro148Gln (c.443C>A) pathogenic?

DES p.Pro148Gln (c.443C>A) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-27). AlphaMissense: ambiguous (0.4673); No allele count reported in gnomAD v4.1 (AN 1,563,890); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Pro148Gln (c.443C>A)?

DES p.Pro148Gln (c.443C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Pro148Gln (c.443C>A) in the general population?

DES p.Pro148Gln (c.443C>A) is no allele count reported in gnomAD v4.1 (AN 1,563,890) (gnomAD).

What do computational predictors say about DES p.Pro148Gln (c.443C>A)?

AlphaMissense predicts ambiguous (score 0.4673) — an in-silico prediction, not a clinical call.

DES p.Pro148Gln

c.443C>A · VCV3501211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4673 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,563,890)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4673	ambiguous
REVEL	0.662	pathogenic-leaning
SaProt	LLR -10.03	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	29.1	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 1,563,890). 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.Pro148Gln
Coding: c.443C>A
MANE Select: NM_001927
Type: single nucleotide variant
Location: chr2:219418905 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 148: the if rod domain; the 'linker 1' 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.Pro148Leu Uncertain significance ★★ ⚠ same residue
DES p.Pro148= Likely benign ★★ same residue
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

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-pro148gln (accessed [today's date]).

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