Is ACBD6 p.Ser15Ile (c.44G>T) pathogenic?

ACBD6 p.Ser15Ile (c.44G>T) is classified Uncertain significance in ACBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely benign (0.2057); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACBD6 p.Ser15Ile (c.44G>T)?

ACBD6 p.Ser15Ile (c.44G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD6 p.Ser15Ile (c.44G>T) in the general population?

ACBD6 p.Ser15Ile (c.44G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACBD6 p.Ser15Ile (c.44G>T)?

AlphaMissense predicts likely benign (score 0.2057) — an in-silico prediction, not a clinical call.

ACBD6 p.Ser15Ile

c.44G>T · VCV3261386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2057 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2057	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -9.18	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 3.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 214 kb · p 0.89 · regional, not allelic
Overall
CADD	24.0	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

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: ACBD6
Protein: p.Ser15Ile
Coding: c.44G>T
MANE Select: NM_032360
Type: single nucleotide variant
Location: chr1:180502223 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 15: the 'disordered' region

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

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
LHX4 p.Ser318Leu 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-ser15ile (accessed [today's date]).

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