Is DECR2 p.Val8Gly (c.23T>G) pathogenic?

DECR2 p.Val8Gly (c.23T>G) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely benign (0.0955); Ultra-rare (popmax 0.039%, afr).

How common is DECR2 p.Val8Gly (c.23T>G) in the general population?

DECR2 p.Val8Gly (c.23T>G) is ultra-rare (popmax 0.039%, afr) (gnomAD).

What do computational predictors say about DECR2 p.Val8Gly (c.23T>G)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

DECR2 p.Val8Gly

c.23T>G · rs566213843 · VCV2211413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.039%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -4.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	24.0	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 0.039% African / African-American · 27/69,222 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0237%

Overall 0.00255% 38/1,491,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.039%	2,564
Remaining individualsnot grpmax-eligible	0.0121%	8,235
European (non-Finnish)	0.000354%	282,135

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.Val8Gly
Coding: c.23T>G
MANE Select: NM_020664
dbSNP: rs566213843
Type: single nucleotide variant
Location: chr16:401986 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.77 · 2 PDB

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

Similar variants

DECR2 p.Val8Met 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-val8gly (accessed [today's date]).

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