Is ACBD6 p.Val28fs (c.82dup) pathogenic?

ACBD6 p.Val28fs (c.82dup) is classified Pathogenic in ACBD6 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-11-18). Very rare (popmax 0.000509%, nfe); Associated with neurodevelopmental disorder with progressive movement abnormalities.

What condition is associated with ACBD6 p.Val28fs (c.82dup)?

ACBD6 p.Val28fs (c.82dup) is associated with neurodevelopmental disorder with progressive movement abnormalities (ClinVar).

How common is ACBD6 p.Val28fs (c.82dup) in the general population?

ACBD6 p.Val28fs (c.82dup) is very rare (popmax 0.000509%, nfe) (gnomAD).

ACBD6 p.Val28fs

c.82dup · rs757566117 · VCV3242364

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

neurodevelopmental disorder with progressive movement abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.29	GERP -4.8

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,882 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,662 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: ACBD6
Protein: p.Val28fs
Coding: c.82dup
MANE Select: NM_032360
dbSNP: rs757566117
Type: Duplication
Location: chr1:180502184 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 28: the 'disordered' region

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 p.Leu121fs Pathogenic ★ same condition
ACBD6 p.Glu63Ter Pathogenic ★ same condition
ACBD6 c.574-2A>G Uncertain significance ★ same condition
ACBD6 p.Val75Phe Uncertain significance ★ ⚠ same condition
ACBD6 p.Asn161_Ile162insTer Pathogenic same condition
ACBD6 p.Asp159fs Pathogenic same condition
LHX4 p.Arg214fs Uncertain significance ★ same type
LHX4 p.Ser244_Ser245insGluSer 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-val28fs (accessed [today's date]).

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