Is DECR2 p.Asp11Asn (c.31G>A) pathogenic?

DECR2 p.Asp11Asn (c.31G>A) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2651); Very rare (popmax 0.00289%, eas).

How common is DECR2 p.Asp11Asn (c.31G>A) in the general population?

DECR2 p.Asp11Asn (c.31G>A) is very rare (popmax 0.00289%, eas) (gnomAD).

What do computational predictors say about DECR2 p.Asp11Asn (c.31G>A)?

AlphaMissense predicts likely benign (score 0.2651) — an in-silico prediction, not a clinical call.

DECR2 p.Asp11Asn

c.31G>A · VCV4659290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00289%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2651	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.1	GERP -0.088, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00289% East Asian · 1/34,570 alleles

Overall 0.000149% 2/1,338,934 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00289%	34,570
European (non-Finnish)	8.86e-05%	1,128,647

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: DECR2
Protein: p.Asp11Asn
Coding: c.31G>A
MANE Select: NM_020664
Type: single nucleotide variant
Location: chr16:401994 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.77 · 2 PDB
Residue 11: a β-strand

Full DECR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DECR2 p.Asp11Gly Uncertain significance ★ ⚠ same residue
DECR2 p.Ala124Thr Uncertain significance ★ ⚠ same type
DECR2 p.Ala129Thr Uncertain significance ★ ⚠ same type
DECR2 p.Ala16Val Uncertain significance ★ ⚠ same type
DECR2 p.Ala178Val Uncertain significance ★ ⚠ same type
DECR2 p.Ala187Val Uncertain significance ★ ⚠ same type
DECR2 p.Ala207Thr Uncertain significance ★ ⚠ same type
DECR2 p.Ala246Thr 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/decr2-p-asp11asn (accessed [today's date]).

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