Is ACBD4 p.Trp193Ter (c.578G>A) pathogenic?

ACBD4 p.Trp193Ter (c.578G>A) is classified Uncertain significance in ACBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). Very rare (popmax 0.00669%, afr).

How common is ACBD4 p.Trp193Ter (c.578G>A) in the general population?

ACBD4 p.Trp193Ter (c.578G>A) is very rare (popmax 0.00669%, afr) (gnomAD).

ACBD4 p.Trp193Ter

c.578G>A · VCV3819329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, afr)

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 8 of 10
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	Δ0.45	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.9	GERP -0.5, phastCons 0.87
Overall
CADD	36.0	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 0.00669% African / African-American · 5/74,716 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000373% 6/1,609,108 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00669%	14,943
Admixed American	0.00167%	59,810

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: ACBD4
Protein: p.Trp193Ter
Coding: c.578G>A
MANE Select: NM_001135705
Type: single nucleotide variant
Location: chr17:45137917 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 1 PDB

Full ACBD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD4 p.Trp193Cys Uncertain significance ★ same residue
ACBD4 c.*20T>A Uncertain significance ★ same type
ACBD4 c.*27A>G Uncertain significance ★ same type
ACBD4 c.*38T>C Uncertain significance ★ same type
ACBD4 c.*3G>A Uncertain significance ★ same type
ACBD4 c.*51T>G Uncertain significance ★ same type
ACBD4 c.*54G>A Uncertain significance ★ same type
ACBD4 p.Ala282= 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/acbd4-p-trp193ter (accessed [today's date]).

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