Is DECR1 p.Arg330Ser (c.990G>C) pathogenic?

DECR1 p.Arg330Ser (c.990G>C) is classified Uncertain significance in DECR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.8353); Absent from gnomAD v4.1.

How common is DECR1 p.Arg330Ser (c.990G>C) in the general population?

DECR1 p.Arg330Ser (c.990G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DECR1 p.Arg330Ser (c.990G>C)?

AlphaMissense predicts likely pathogenic (score 0.8353) — an in-silico prediction, not a clinical call.

DECR1 p.Arg330Ser

c.990G>C · VCV4659285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8353 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8353	likely pathogenic
REVEL	0.698	pathogenic-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 50 kb · p 0.26 · regional, not allelic
Overall
CADD	22.9	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

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: DECR1
Protein: p.Arg330Ser
Coding: c.990G>C
MANE Select: NM_001359
Type: single nucleotide variant
Location: chr8:90051879 (GRCh38)
Gene constraint: LOEUF 1.566 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.20 · 3 PDB

Full DECR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DECR1 p.Ala20Thr Uncertain significance ★★ ⚠ same type
DECR1 p.Val207Leu Uncertain significance ★★ ⚠ same type
DECR1 p.Ser26Asn Likely benign ★★ ⚠ same type
DECR1 p.Ala173Val Uncertain significance ★ ⚠ same type
DECR1 p.Ala225Glu Uncertain significance ★ ⚠ same type
DECR1 p.Ala278Thr Uncertain significance ★ ⚠ same type
DECR1 p.Arg251Cys Uncertain significance ★ ⚠ same type
DECR1 p.Arg251His Uncertain significance ★ ⚠ same type

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/decr1-p-arg330ser (accessed [today's date]).

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