Is ACBD3 p.Glu455Asp (c.1365G>C) pathogenic?

ACBD3 p.Glu455Asp (c.1365G>C) is classified Uncertain significance in ACBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0651); Rare (popmax 0.108%, amr).

How common is ACBD3 p.Glu455Asp (c.1365G>C) in the general population?

ACBD3 p.Glu455Asp (c.1365G>C) is rare (popmax 0.108%, amr) (gnomAD).

What do computational predictors say about ACBD3 p.Glu455Asp (c.1365G>C)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

ACBD3 p.Glu455Asp

c.1365G>C · rs201638495 · VCV2220119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.83	GERP -2.8, phastCons 0.003
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 0.00022 · regional, not allelic
Overall
CADD	16.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% Admixed American · 65/60,010 alleles

Filtering AF 0.0872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0795%

Overall 0.0398% 642/1,613,940 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.108%	923
Remaining individualsnot grpmax-eligible	0.0576%	1,735
European (non-Finnish)	0.0447%	2,235
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,920
Middle Eastern	0.0167%	6,006
African / African-American	0.00534%	18,730
East Asian	0.00223%	44,900
Finnishnot grpmax-eligible	0.00156%	64,046
South Asian	0.0011%	91,076

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: ACBD3
Protein: p.Glu455Asp
Coding: c.1365G>C
MANE Select: NM_022735
dbSNP: rs201638495
Type: single nucleotide variant
Location: chr1:226152345 (GRCh38)
Gene constraint: LOEUF 0.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50 · 12 PDB
Residue 455: the gold domain

Full ACBD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD3 p.Glu455Lys Uncertain significance ★ ⚠ same residue
ACBD3 p.Ala177Glu Uncertain significance ★ ⚠ same type
ACBD3 p.Ala177Val Uncertain significance ★ ⚠ same type
ACBD3 p.Ala371Val Uncertain significance ★ ⚠ same type
ACBD3 p.Ala3Thr Uncertain significance ★ ⚠ same type
ACBD3 p.Ala442Asp Uncertain significance ★ ⚠ same type
ACBD3 p.Ala63Val Uncertain significance ★ ⚠ same type
ACBD3 p.Ala90Gly 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/acbd3-p-glu455asp (accessed [today's date]).

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