Is DECR2 p.Val8Met (c.22G>A) pathogenic?

DECR2 p.Val8Met (c.22G>A) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.2203); Ultra-rare (popmax 0.081%, afr).

How common is DECR2 p.Val8Met (c.22G>A) in the general population?

DECR2 p.Val8Met (c.22G>A) is ultra-rare (popmax 0.081%, afr) (gnomAD).

What do computational predictors say about DECR2 p.Val8Met (c.22G>A)?

AlphaMissense predicts likely benign (score 0.2203) — an in-silico prediction, not a clinical call.

DECR2 p.Val8Met

c.22G>A · rs201237938 · VCV2463043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2203 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.081%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2203	likely benign
REVEL	0.402	indeterminate
SaProt	LLR -7.33	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 6.2	GERP -0.088, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	24.2	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 0.081% African / African-American · 56/69,130 alleles

Filtering AF 0.0641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00436% 65/1,491,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.081%	1,234
Middle Eastern	0.0186%	5,384
Remaining individualsnot grpmax-eligible	0.00694%	14,408
Admixed American	0.00228%	43,834
Finnishnot grpmax-eligible	0.00223%	44,908
European (non-Finnish)	0.000177%	564,302

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.Val8Met
Coding: c.22G>A
MANE Select: NM_020664
dbSNP: rs201237938
Type: single nucleotide variant
Location: chr16:401985 (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.Val8Gly 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-val8met (accessed [today's date]).

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