Is DERL1 p.Ala37Pro (c.109G>C) pathogenic?

DERL1 p.Ala37Pro (c.109G>C) is classified Uncertain significance in DERL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.3003); Very rare (popmax 8.48e-05%, nfe).

How common is DERL1 p.Ala37Pro (c.109G>C) in the general population?

DERL1 p.Ala37Pro (c.109G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DERL1 p.Ala37Pro (c.109G>C)?

AlphaMissense predicts likely benign (score 0.3003) — an in-silico prediction, not a clinical call.

DERL1 p.Ala37Pro

c.109G>C · VCV4239694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3003	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.91, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 0.0022 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,862 alleles

Overall 6.84e-05% 1/1,461,460 alleles · very rare

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: DERL1
Protein: p.Ala37Pro
Coding: c.109G>C
MANE Select: NM_024295
Type: single nucleotide variant
Location: chr8:123042014 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.76 · 6 PDB

Full DERL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DERL1 p.Ala45Val Uncertain significance ★ ⚠ same type
DERL1 p.Ala96Val Uncertain significance ★ ⚠ same type
DERL1 p.Arg208His Uncertain significance ★ ⚠ same type
DERL1 p.Asp193His Uncertain significance ★ ⚠ same type
DERL1 p.Asp250Asn Uncertain significance ★ ⚠ same type
DERL1 p.Gln204Arg Uncertain significance ★ ⚠ same type
DERL1 p.Gly215Val Uncertain significance ★ ⚠ same type
DERL1 p.Gly236Arg 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/derl1-p-ala37pro (accessed [today's date]).

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