Is ADGRD1 p.Ala381Ser (c.1141G>T) pathogenic?

ADGRD1 p.Ala381Ser (c.1141G>T) is classified Uncertain significance in ADGRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.3297); Absent from gnomAD v4.1.

How common is ADGRD1 p.Ala381Ser (c.1141G>T) in the general population?

ADGRD1 p.Ala381Ser (c.1141G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRD1 p.Ala381Ser (c.1141G>T)?

AlphaMissense predicts likely benign (score 0.3297) — an in-silico prediction, not a clinical call.

ADGRD1 p.Ala381Ser

c.1141G>T · VCV4239031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3297 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3297	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 185 kb · p 0.0023 · regional, not allelic
Overall
CADD	23.9	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

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: ADGRD1
Protein: p.Ala381Ser
Coding: c.1141G>T
MANE Select: NM_198827
Type: single nucleotide variant
Location: chr12:131003299 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 8 PDB
Residue 381: the gain-b domain

Full ADGRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRD1 p.Pro165Ala Uncertain significance ★★ ⚠ same type
ADGRD1 p.Ala124Thr Uncertain significance ★ ⚠ same type
ADGRD1 p.Ala124Val Uncertain significance ★ ⚠ same type
ADGRD1 p.Ala40Val Uncertain significance ★ ⚠ same type
ADGRD1 p.Ala565Val Uncertain significance ★ ⚠ same type
ADGRD1 p.Ala648Val Uncertain significance ★ ⚠ same type
ADGRD1 p.Ala709Val Uncertain significance ★ ⚠ same type
ADGRD1 p.Arg150Gln 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/adgrd1-p-ala381ser (accessed [today's date]).

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