Is ACBD4 p.Ala282= (c.846G>A) pathogenic?

ACBD4 p.Ala282= (c.846G>A) is classified Uncertain significance in ACBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). Very rare (popmax 0.00314%, nfe).

How common is ACBD4 p.Ala282= (c.846G>A) in the general population?

ACBD4 p.Ala282= (c.846G>A) is very rare (popmax 0.00314%, nfe) (gnomAD).

ACBD4 p.Ala282=

c.846G>A · rs371852063 · VCV2553198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP -2.1, phastCons 0.17
Overall
CADD	7.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,179,978 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00248% 40/1,613,632 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,891
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,472
Finnishnot grpmax-eligible	0.00157%	63,706

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.Ala282=
Coding: c.846G>A
MANE Select: NM_001135705
dbSNP: rs371852063
Type: single nucleotide variant
Location: chr17:45143499 (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.Ala282Glu 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.Ala72Thr 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-ala282 (accessed [today's date]).

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