Is DECR1 p.Ala173Val (c.518C>T) pathogenic?

DECR1 p.Ala173Val (c.518C>T) is classified Uncertain significance in DECR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.2442); Ultra-rare (popmax 0.0182%, eas).

How common is DECR1 p.Ala173Val (c.518C>T) in the general population?

DECR1 p.Ala173Val (c.518C>T) is ultra-rare (popmax 0.0182%, eas) (gnomAD).

What do computational predictors say about DECR1 p.Ala173Val (c.518C>T)?

AlphaMissense predicts likely benign (score 0.2442) — an in-silico prediction, not a clinical call.

DECR1 p.Ala173Val

c.518C>T · VCV3500742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2442 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2442	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 50 kb · p 0.26 · regional, not allelic
Overall
CADD	21.3	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 0.0182% East Asian · 8/44,044 alleles

Filtering AF 0.00898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00651%

Overall 0.000901% 13/1,442,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0182%	5,505
Remaining individualsnot grpmax-eligible	0.00324%	30,879
South Asian	0.00115%	86,716
European (non-Finnish)	0.00017%	586,854

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.Ala173Val
Coding: c.518C>T
MANE Select: NM_001359
Type: single nucleotide variant
Location: chr8:90021009 (GRCh38)
Gene constraint: LOEUF 1.566 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.20 · 3 PDB
Residue 173: an α-helix

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

Similar variants

DECR1 p.Ala20Thr Uncertain significance ★★ ⚠ same type
DECR1 p.Val207Leu Uncertain significance ★★ ⚠ same type
DECR1 p.Ser26Asn Likely benign ★★ ⚠ same type
DECR1 p.Ala225Glu Uncertain significance ★ ⚠ same type
DECR1 p.Ala278Thr Uncertain significance ★ ⚠ same type
DECR1 p.Arg251Cys Uncertain significance ★ ⚠ same type
DECR1 p.Arg251His Uncertain significance ★ ⚠ same type
DECR1 p.Arg270Cys 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-ala173val (accessed [today's date]).

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