Is ACBD6 p.Glu63Ter (c.187G>T) pathogenic?

ACBD6 p.Glu63Ter (c.187G>T) is classified Pathogenic in ACBD6 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-03-21). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with progressive movement abnormalities.

What condition is associated with ACBD6 p.Glu63Ter (c.187G>T)?

ACBD6 p.Glu63Ter (c.187G>T) is associated with neurodevelopmental disorder with progressive movement abnormalities (ClinVar).

How common is ACBD6 p.Glu63Ter (c.187G>T) in the general population?

ACBD6 p.Glu63Ter (c.187G>T) is absent from gnomAD v4.1 (gnomAD).

ACBD6 p.Glu63Ter

c.187G>T · rs2525656325 · VCV3242366

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodevelopmental disorder with progressive movement abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	Δ0.56	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Overall
CADD	55.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: ACBD6
Protein: p.Glu63Ter
Coding: c.187G>T
MANE Select: NM_032360
dbSNP: rs2525656325
Type: single nucleotide variant
Location: chr1:180502080 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 63: the acb domain; a UniProt-annotated variant site (in nedpm; pathogenic); an α-helix

Full ACBD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with progressive movement abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACBD6 c.574-2A>G Uncertain significance ★ same condition
ACBD6 p.Val75Phe Uncertain significance ★ ⚠ same condition
ACBD6 p.Leu121fs Pathogenic ★ same condition
ACBD6 p.Asn161_Ile162insTer Pathogenic same condition
ACBD6 p.Asp159fs Pathogenic same condition
ACBD6 p.Val28fs Pathogenic same condition
LHX4 c.*17C>T Uncertain significance ★★ same type
LHX4 p.Ala354Val 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/acbd6-p-glu63ter (accessed [today's date]).

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