Is ACBD4 p.Arg204His (c.611G>A) pathogenic?

ACBD4 p.Arg204His (c.611G>A) is classified Uncertain significance in ACBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: likely benign (0.0908); Ultra-rare (popmax 0.0223%, eas).

How common is ACBD4 p.Arg204His (c.611G>A) in the general population?

ACBD4 p.Arg204His (c.611G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about ACBD4 p.Arg204His (c.611G>A)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

ACBD4 p.Arg204His

c.611G>A · rs760081117 · VCV3135921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.37	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 -0.4	GERP -3.4
Regional constraint	o/e 1.02	unconstrained · MANE · 6,861 bp · p 0.72 · regional, not allelic
Overall
CADD	2.488	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V201M vs ClinVar R204H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,890 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00105% 17/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,056
European (non-Finnish)	0.000424%	236,003

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.Arg204His
Coding: c.611G>A
MANE Select: NM_001135705
dbSNP: rs760081117
Type: single nucleotide variant
Location: chr17:45137950 (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.Arg204Ser Uncertain significance ★ ⚠ same residue
ACBD4 p.Arg204Cys Likely benign ★ 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

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-arg204his (accessed [today's date]).

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