Is DECR1 p.Val175Met (c.523G>A) pathogenic?

DECR1 p.Val175Met (c.523G>A) is classified Likely benign in DECR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). AlphaMissense: likely benign (0.237); Ultra-rare (popmax 0.0831%, mid).

How common is DECR1 p.Val175Met (c.523G>A) in the general population?

DECR1 p.Val175Met (c.523G>A) is ultra-rare (popmax 0.0831%, mid) (gnomAD).

What do computational predictors say about DECR1 p.Val175Met (c.523G>A)?

AlphaMissense predicts likely benign (score 0.237) — an in-silico prediction, not a clinical call.

DECR1 p.Val175Met

c.523G>A · rs372630127 · VCV2391458

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.237 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0831%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.237	likely benign
REVEL	0.471	indeterminate
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.35, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 50 kb · p 0.26 · regional, not allelic
Overall
CADD	17.99	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 0.0831% Middle Eastern · 5/6,020 alleles

Filtering AF 0.0327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0211%

Overall 0.0069% 110/1,593,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0831%	1,204
Admixed American	0.0257%	3,897
South Asian	0.0185%	5,403
Remaining individualsnot grpmax-eligible	0.0146%	6,857
European (non-Finnish)	0.00537%	18,629
African / African-American	0.00272%	36,799
Finnishnot grpmax-eligible	0.00157%	63,838

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.Val175Met
Coding: c.523G>A
MANE Select: NM_001359
dbSNP: rs372630127
Type: single nucleotide variant
Location: chr8:90021014 (GRCh38)
Gene constraint: LOEUF 1.566 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.20 · 3 PDB
Residue 175: 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.Ala173Val Uncertain significance ★ ⚠ 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

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-val175met (accessed [today's date]).

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