Is ACBD5 c.1565+2T>A pathogenic?

ACBD5 c.1565+2T>A is classified Uncertain significance in ACBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). Absent from gnomAD v4.1; Associated with retinal dystrophy with leukodystrophy.

What condition is associated with ACBD5 c.1565+2T>A?

ACBD5 c.1565+2T>A is associated with retinal dystrophy with leukodystrophy (ClinVar).

How common is ACBD5 c.1565+2T>A in the general population?

ACBD5 c.1565+2T>A is absent from gnomAD v4.1 (gnomAD).

ACBD5 c.1565+2T>A

rs2540389570 · VCV2438826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinal dystrophy with leukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.98	donor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.89	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: ACBD5
Coding: c.1565+2T>A
MANE Select: NM_145698
dbSNP: rs2540389570
Type: single nucleotide variant
Location: chr10:27204438 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB

Full ACBD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinal dystrophy with leukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same condition
ACBD5 c.15+54G>T Benign ★★ same condition
ACBD5 c.491-51A>G Benign ★★ same condition
ACBD5 p.Pro173= Benign ★★ same condition
ACBD5 c.936+1G>A Likely pathogenic ★ same condition
ACBD5 p.Glu393Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
ACBD5 p.Leu476Ser Uncertain significance ★ ⚠ same condition
ACBD5 p.Ser41Tyr 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/acbd5-c-1565-plus-2t-a (accessed [today's date]).

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