Is DECR2 p.Arg78Trp (c.232C>T) pathogenic?

DECR2 p.Arg78Trp (c.232C>T) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.1778); Ultra-rare (popmax 0.0453%, afr).

How common is DECR2 p.Arg78Trp (c.232C>T) in the general population?

DECR2 p.Arg78Trp (c.232C>T) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about DECR2 p.Arg78Trp (c.232C>T)?

AlphaMissense predicts likely benign (score 0.1778) — an in-silico prediction, not a clinical call.

DECR2 p.Arg78Trp

c.232C>T · rs374820826 · VCV2600150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1778	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -11.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.5, phastCons 0.81
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.0453% African / African-American · 34/75,044 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.00354% 57/1,611,672 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Admixed American	0.0133%	7,497
Remaining individualsnot grpmax-eligible	0.00321%	31,191
European (non-Finnish)	0.0011%	90,718

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.Arg78Trp
Coding: c.232C>T
MANE Select: NM_020664
dbSNP: rs374820826
Type: single nucleotide variant
Location: chr16:407455 (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

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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
DECR2 p.Ala96Thr 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-arg78trp (accessed [today's date]).

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