Is ACBD6 p.Asp23fs (c.63_64del) pathogenic?

ACBD6 p.Asp23fs (c.6364del) is classified Pathogenic in ACBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). Very rare (popmax 0.00667%, amr).

How common is ACBD6 p.Asp23fs (c.63_64del) in the general population?

ACBD6 p.Asp23fs (c.63_64del) is very rare (popmax 0.00667%, amr) (gnomAD).

ACBD6 p.Asp23fs

c.63_64del · VCV3363383

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 0.76	GERP -0.42, phastCons 0.99
Overall
CADD	34.0	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

Grpmax group 0.00667% Admixed American · 4/60,012 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00223% 36/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,003
European (non-Finnish)	0.00254%	39,335
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Asp23fs
Coding: c.63_64del
MANE Select: NM_032360
Type: Deletion
Location: chr1:180502203 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 23: the 'disordered' region

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

Similar variants

LHX4 p.Glu241del Uncertain significance ★★ same type
LHX4 p.Lys242del Benign/Likely benign ★★ same type
LHX4 p.Asn328fs Uncertain significance ★ same type
LHX4 p.Gly358del Uncertain significance ★ same type
ACBD6 c.664-9del Likely benign ★ same type
ACBD6 p.Asn161_Ile162insTer Pathogenic same type
ACBD6 p.Asp159fs Pathogenic 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-asp23fs (accessed [today's date]).

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