Is ACBD3 p.Arg197Ser (c.591G>C) pathogenic?

ACBD3 p.Arg197Ser (c.591G>C) is classified Uncertain significance in ACBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: ambiguous (0.486); Very rare (popmax 0.00332%, nfe).

How common is ACBD3 p.Arg197Ser (c.591G>C) in the general population?

ACBD3 p.Arg197Ser (c.591G>C) is very rare (popmax 0.00332%, nfe) (gnomAD).

What do computational predictors say about ACBD3 p.Arg197Ser (c.591G>C)?

AlphaMissense predicts ambiguous (score 0.486) — an in-silico prediction, not a clinical call.

ACBD3 p.Arg197Ser

c.591G>C · VCV3474837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00332%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.486	ambiguous
REVEL	0.162	moderately benign-leaning
SaProt	LLR -13.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP 0.81, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 0.00022 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00332% European (non-Finnish) · 39/1,174,132 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00256% 41/1,601,996 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00332%	30,106
Remaining individualsnot grpmax-eligible	0.00161%	61,956
African / African-American	0.00135%	74,236

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.Arg197Ser
Coding: c.591G>C
MANE Select: NM_022735
Type: single nucleotide variant
Location: chr1:226161668 (GRCh38)
Gene constraint: LOEUF 0.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50 · 12 PDB
Residue 197: the 'charged amino-acid region (car)' region; the 'disordered' region

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

Similar variants

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
ACBD3 p.Ala90Thr 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-arg197ser (accessed [today's date]).

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