Is ACBD5 p.Arg342His (c.1025G>A) pathogenic?

ACBD5 p.Arg342His (c.1025G>A) is classified Conflicting classifications of pathogenicity in ACBD5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-07-17). AlphaMissense: likely benign (0.0682); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with ACBD5 p.Arg342His (c.1025G>A)?

ACBD5 p.Arg342His (c.1025G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD5 p.Arg342His (c.1025G>A) in the general population?

ACBD5 p.Arg342His (c.1025G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ACBD5 p.Arg342His (c.1025G>A)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

ACBD5 p.Arg342His

c.1025G>A · rs751802868 · VCV1036581

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.29	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 4.4	GERP -1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	12.12	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R351H vs ClinVar R342H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000867% 14/1,613,938 alleles · ultra-rare exomes 13/1,461,892 · genomes 1/152,046 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.005%	19,989
East Asian	0.00223%	44,884
African / African-American	0.00134%	74,876
South Asian	0.0011%	91,082
European (non-Finnish)	0.000593%	168,577

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: ACBD5
Protein: p.Arg342His
Coding: c.1025G>A
MANE Select: NM_145698
dbSNP: rs751802868
Type: single nucleotide variant
Location: chr10:27210993 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB

Full ACBD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACBD5 p.Arg342Cys Uncertain significance ★ ⚠ same residue
ACBD5 p.Ala182Thr Uncertain significance ★★ ⚠ same condition
ACBD5 p.Arg384Trp Uncertain significance ★★ ⚠ same condition
ACBD5 p.Arg415Trp Uncertain significance ★★ ⚠ same condition
ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same condition
ACBD5 p.Gln452His Uncertain significance ★★ ⚠ same condition
ACBD5 p.Glu312Lys Uncertain significance ★★ ⚠ same condition
ACBD5 p.Glu493Lys Uncertain significance ★★ ⚠ same condition

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/acbd5-p-arg342his (accessed [today's date]).

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