Is DERL1 p.Ala96Val (c.287C>T) pathogenic?

DERL1 p.Ala96Val (c.287C>T) is classified Uncertain significance in DERL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.9596); Absent from gnomAD v4.1.

How common is DERL1 p.Ala96Val (c.287C>T) in the general population?

DERL1 p.Ala96Val (c.287C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DERL1 p.Ala96Val (c.287C>T)?

AlphaMissense predicts likely pathogenic (score 0.9596) — an in-silico prediction, not a clinical call.

DERL1 p.Ala96Val

c.287C>T · VCV4239701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9596 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9596	likely pathogenic
REVEL	0.51	indeterminate
SaProt	LLR -12.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Pangolin	Δ0.24	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 0.0022 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DERL1
Protein: p.Ala96Val
Coding: c.287C>T
MANE Select: NM_024295
Type: single nucleotide variant
Location: chr8:123025029 (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.Ala37Pro Uncertain significance ★ ⚠ same type
DERL1 p.Ala45Val 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-ala96val (accessed [today's date]).

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