Is DECR2 p.Phe285Leu (c.855C>G) pathogenic?

DECR2 p.Phe285Leu (c.855C>G) is classified Uncertain significance in DECR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: ambiguous (0.5273); Ultra-rare (popmax 0.0142%, nfe).

How common is DECR2 p.Phe285Leu (c.855C>G) in the general population?

DECR2 p.Phe285Leu (c.855C>G) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

What do computational predictors say about DECR2 p.Phe285Leu (c.855C>G)?

AlphaMissense predicts ambiguous (score 0.5273) — an in-silico prediction, not a clinical call.

DECR2 p.Phe285Leu

c.855C>G · rs370013477 · VCV3081252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5273 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5273	ambiguous
REVEL	0.209	benign-leaning
SaProt	LLR -4.71	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3.5
Regional constraint	o/e 1.14	unconstrained · MANE · 9,611 bp · p 0.0038 · regional, not allelic
Overall
CADD	0.022	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 0.0142% European (non-Finnish) · 168/1,179,766 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0117% 188/1,613,436 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0272%	3,674
European (non-Finnish)grpmax	0.0142%	7,022
African / African-American	0.004%	24,983

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe285Leu
Coding: c.855C>G
MANE Select: NM_020664
dbSNP: rs370013477
Type: single nucleotide variant
Location: chr16:411554 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.77 · 2 PDB

Full DECR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DECR2 p.Phe285= Likely benign ★ same residue
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.Ala187Val Uncertain significance ★ ⚠ same type
DECR2 p.Ala207Thr Uncertain significance ★ ⚠ same type
DECR2 p.Ala246Thr 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-phe285leu (accessed [today's date]).

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