Is DECR2 p.Ala187Val (c.560C>T) pathogenic?

DECR2 p.Ala187Val (c.560C>T) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.3722); Ultra-rare (popmax 0.0295%, eas).

How common is DECR2 p.Ala187Val (c.560C>T) in the general population?

DECR2 p.Ala187Val (c.560C>T) is ultra-rare (popmax 0.0295%, eas) (gnomAD).

What do computational predictors say about DECR2 p.Ala187Val (c.560C>T)?

AlphaMissense predicts ambiguous (score 0.3722) — an in-silico prediction, not a clinical call.

DECR2 p.Ala187Val

c.560C>T · rs765990942 · VCV2524919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3722 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0295%, eas)

Computational evidence

Protein change
AlphaMissense	0.3722	ambiguous
REVEL	0.423	indeterminate
SaProt	LLR -9.45	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	23.2	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 0.0295% East Asian · 13/44,054 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00182% 29/1,596,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0295%	3,389
South Asian	0.00566%	17,660
African / African-American	0.00268%	37,281
Admixed American	0.00173%	57,640
European (non-Finnish)	0.000683%	146,484

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.Ala187Val
Coding: c.560C>T
MANE Select: NM_020664
dbSNP: rs765990942
Type: single nucleotide variant
Location: chr16:410975 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.77 · 2 PDB
Residue 187: 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.Ala207Thr Uncertain significance ★ ⚠ same type
DECR2 p.Ala246Thr Uncertain significance ★ ⚠ same type
DECR2 p.Ala96Thr Uncertain significance ★ ⚠ same type
DECR2 p.Arg146His 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-ala187val (accessed [today's date]).

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