Is ACBD6 p.His151Pro (c.452A>C) pathogenic?

ACBD6 p.His151Pro (c.452A>C) is classified Uncertain significance in ACBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). AlphaMissense: likely benign (0.2615); Ultra-rare (popmax 0.0133%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACBD6 p.His151Pro (c.452A>C)?

ACBD6 p.His151Pro (c.452A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD6 p.His151Pro (c.452A>C) in the general population?

ACBD6 p.His151Pro (c.452A>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about ACBD6 p.His151Pro (c.452A>C)?

AlphaMissense predicts likely benign (score 0.2615) — an in-silico prediction, not a clinical call.

ACBD6 p.His151Pro

c.452A>C · rs1298842306 · VCV2469733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2615	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -4.75	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 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 214 kb · p 0.89 · regional, not allelic
Overall
CADD	23.3	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,992 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000496% 8/1,612,960 alleles · ultra-rare

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: ACBD6
Protein: p.His151Pro
Coding: c.452A>C
MANE Select: NM_032360
dbSNP: rs1298842306
Type: single nucleotide variant
Location: chr1:180430195 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 151: a UniProt-annotated variant site (in nedpm; pathogenic)

Full ACBD6 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

ACBD6 p.His151Arg Uncertain significance ★ ⚠ same residue
LHX4 p.Ala354Val Uncertain significance ★★ ⚠ same condition
LHX4 p.Arg161Gln Uncertain significance ★★ ⚠ same condition
LHX4 p.Gly283Arg Uncertain significance ★★ ⚠ same condition
LHX4 p.His387Gln Uncertain significance ★★ ⚠ same condition
LHX4 p.Leu338Trp Uncertain significance ★★ ⚠ same condition
LHX4 p.Met286Thr Uncertain significance ★★ ⚠ same condition
LHX4 p.Ser230Asn 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/acbd6-p-his151pro (accessed [today's date]).

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