Is ACBD4 p.Pro213Arg (c.638C>G) pathogenic?

ACBD4 p.Pro213Arg (c.638C>G) is classified Uncertain significance in ACBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.0595); Very rare (popmax 0.005%, amr).

How common is ACBD4 p.Pro213Arg (c.638C>G) in the general population?

ACBD4 p.Pro213Arg (c.638C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ACBD4 p.Pro213Arg (c.638C>G)?

AlphaMissense predicts likely benign (score 0.0595) — an in-silico prediction, not a clinical call.

ACBD4 p.Pro213Arg

c.638C>G · rs1433591964 · VCV2237075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0595	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -6.27	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 -0.16	GERP 1.7
Regional constraint	o/e 1.02	unconstrained · MANE · 6,861 bp · p 0.72 · regional, not allelic
Overall
CADD	10.07	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 P210A vs ClinVar P213R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,966 alleles

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

Overall 0.000342% 5/1,461,134 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,989
European (non-Finnish)	0.00017%	589,932

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.Pro213Arg
Coding: c.638C>G
MANE Select: NM_001135705
dbSNP: rs1433591964
Type: single nucleotide variant
Location: chr17:45137977 (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 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
ACBD4 p.Ala282= Uncertain significance ★ same type
ACBD4 p.Ala282Glu 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-pro213arg (accessed [today's date]).

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