Is DECR2 p.Arg170Trp (c.508C>T) pathogenic?

DECR2 p.Arg170Trp (c.508C>T) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). AlphaMissense: likely benign (0.3124); Ultra-rare (popmax 0.0203%, mid).

How common is DECR2 p.Arg170Trp (c.508C>T) in the general population?

DECR2 p.Arg170Trp (c.508C>T) is ultra-rare (popmax 0.0203%, mid) (gnomAD).

What do computational predictors say about DECR2 p.Arg170Trp (c.508C>T)?

AlphaMissense predicts likely benign (score 0.3124) — an in-silico prediction, not a clinical call.

DECR2 p.Arg170Trp

c.508C>T · rs747400979 · VCV3081242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3124	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP -0.54, phastCons 0.23
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	21.5	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 0.0203% Middle Eastern · 1/4,918 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00155% 25/1,607,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0203%	4,918
Admixed American	0.00672%	14,870
East Asian	0.00224%	44,722
European (non-Finnish)	0.00153%	65,488
African / African-American	0.00134%	74,846

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.Arg170Trp
Coding: c.508C>T
MANE Select: NM_020664
dbSNP: rs747400979
Type: single nucleotide variant
Location: chr16:410736 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.77 · 2 PDB
Residue 170: an α-helix

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

Similar variants

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
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-arg170trp (accessed [today's date]).

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