Is DERL3 p.Pro152Leu (c.455C>T) pathogenic?

DERL3 p.Pro152Leu (c.455C>T) is classified Uncertain significance in DERL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: ambiguous (0.4232); Ultra-rare (popmax 0.0147%, afr).

How common is DERL3 p.Pro152Leu (c.455C>T) in the general population?

DERL3 p.Pro152Leu (c.455C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about DERL3 p.Pro152Leu (c.455C>T)?

AlphaMissense predicts ambiguous (score 0.4232) — an in-silico prediction, not a clinical call.

DERL3 p.Pro152Leu

c.455C>T · VCV4239706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4232 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Computational evidence

Protein change
AlphaMissense	0.4232	ambiguous
REVEL	0.471	indeterminate
SaProt	LLR -13.51	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,115 bp · p 0.39 · regional, not allelic
Overall
CADD	33.0	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 0.0147% African / African-American · 11/75,048 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00632%

Overall 0.00217% 35/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,823
Admixed American	0.00333%	30,012
European (non-Finnish)	0.00178%	56,191
South Asian	0.0011%	91,082

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: DERL3
Protein: p.Pro152Leu
Coding: c.455C>T
MANE Select: NM_003073 · reported on NM_001002862
Type: single nucleotide variant
Location: chr22:23837727 (GRCh38)

Full DERL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/derl3-p-pro152leu (accessed [today's date]).

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