Is ACBD4 p.Arg204Ser (c.610C>A) pathogenic?

ACBD4 p.Arg204Ser (c.610C>A) is classified Uncertain significance in ACBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.1717); Absent from gnomAD v4.1.

How common is ACBD4 p.Arg204Ser (c.610C>A) in the general population?

ACBD4 p.Arg204Ser (c.610C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACBD4 p.Arg204Ser (c.610C>A)?

AlphaMissense predicts likely benign (score 0.1717) — an in-silico prediction, not a clinical call.

ACBD4 p.Arg204Ser

c.610C>A · VCV3476118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1717 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1717	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.16	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 -0.58	GERP -1.9
Regional constraint	o/e 1.02	unconstrained · MANE · 6,861 bp · p 0.72 · regional, not allelic
Overall
CADD	0.207	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 S200R vs ClinVar R204S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACBD4
Protein: p.Arg204Ser
Coding: c.610C>A
MANE Select: NM_001135705
Type: single nucleotide variant
Location: chr17:45137949 (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.Arg204His 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-arg204ser (accessed [today's date]).

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