Is DECR2 p.Ala129Thr (c.385G>A) pathogenic?

DECR2 p.Ala129Thr (c.385G>A) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely pathogenic (0.6796); Very rare (popmax 0.00439%, sas).

How common is DECR2 p.Ala129Thr (c.385G>A) in the general population?

DECR2 p.Ala129Thr (c.385G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DECR2 p.Ala129Thr (c.385G>A)?

AlphaMissense predicts likely pathogenic (score 0.6796) — an in-silico prediction, not a clinical call.

DECR2 p.Ala129Thr

c.385G>A · VCV4239131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6796	likely pathogenic
REVEL	0.47	indeterminate
SaProt	LLR -14.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00439% South Asian · 4/91,072 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000744% 12/1,613,598 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,768
East Asian	0.00223%	44,892
African / African-American	0.00134%	74,884
European (non-Finnish)	0.000509%	196,652

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.Ala129Thr
Coding: c.385G>A
MANE Select: NM_020664
Type: single nucleotide variant
Location: chr16:410290 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.77 · 2 PDB
Residue 129: 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.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
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-ala129thr (accessed [today's date]).

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