Is DECR1 p.Asp122= (c.366T>C) pathogenic?

DECR1 p.Asp122= (c.366T>C) is classified Benign in DECR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-22). Rare (popmax 0.79%, afr); Associated with progressive encephalopathy with leukodystrophy due to DECR deficiency.

What condition is associated with DECR1 p.Asp122= (c.366T>C)?

DECR1 p.Asp122= (c.366T>C) is associated with progressive encephalopathy with leukodystrophy due to DECR deficiency (ClinVar).

How common is DECR1 p.Asp122= (c.366T>C) in the general population?

DECR1 p.Asp122= (c.366T>C) is rare (popmax 0.79%, afr) (gnomAD).

DECR1 p.Asp122=

Q: How is Progressive encephalopathy with leukodystrophy due to DECR deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.366T>C · rs138725804 · VCV697432

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.79%, afr)

Conditions

progressive encephalopathy with leukodystrophy due to DECR deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -4.4
Overall
CADD	0.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.79% African / African-American · 593/75,040 alleles

Filtering AF 0.738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.717%

Overall 0.0513% 828/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.79%	127
Middle Eastern	0.214%	466
Ashkenazi Jewishnot grpmax-eligible	0.132%	759
Admixed American	0.0949%	1,053
Remaining individualsnot grpmax-eligible	0.0832%	1,202
South Asian	0.0121%	8,281
European (non-Finnish)	0.00534%	18,731

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: DECR1
Protein: p.Asp122=
Coding: c.366T>C
MANE Select: NM_001359
dbSNP: rs138725804
Type: single nucleotide variant
Location: chr8:90019121 (GRCh38)
Gene constraint: LOEUF 1.566 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.20 · 3 PDB
Residue 122: an α-helix

Full DECR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive encephalopathy with leukodystrophy due to DECR deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive encephalopathy with leukodystrophy due to DECR deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DECR1 p.Ala20Thr Uncertain significance ★★ ⚠ same condition
DECR1 p.Val207Leu Uncertain significance ★★ ⚠ same condition
DECR1 p.Ser26Asn Likely benign ★★ ⚠ same condition
DECR1 p.Gly68Ser Uncertain significance ★ ⚠ same condition
DECR1 p.Asn144= Benign ★ same condition
DECR1 p.Pro240Leu Likely benign ★ same condition
DECR1 c.885+9del Benign ★ same condition
DECR1 p.Ala173Val 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/decr1-p-asp122 (accessed [today's date]).

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