Is ACBD5 p.Pro173= (c.519A>G) pathogenic?

ACBD5 p.Pro173= (c.519A>G) is classified Benign in ACBD5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 52.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with retinal dystrophy with leukodystrophy.

What condition is associated with ACBD5 p.Pro173= (c.519A>G)?

ACBD5 p.Pro173= (c.519A>G) is associated with retinal dystrophy with leukodystrophy (ClinVar).

ACBD5 p.Pro173=

Q: How common is ACBD5 p.Pro173= (c.519A>G) in the general population?

ACBD5 p.Pro173= (c.519A>G) is common (popmax 52.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.519A>G · rs10764690 · VCV1166118

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 52.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

retinal dystrophy with leukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.45, phastCons 1
Overall
CADD	12.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.5% European (non-Finnish) · 619,275/1,179,536 alleles

Filtering AF 52.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.3%

Overall 48.6% 784,216/1,613,318 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	52.5%	2
Finnishnot grpmax-eligible	50.6%	2
Amishnot grpmax-eligible	48.8%	2
Remaining individualsnot grpmax-eligible	46.3%	2
Admixed American	43.4%	2
Ashkenazi Jewishnot grpmax-eligible	41.3%	2
East Asian	39.7%	3
South Asian	37.7%	3
Middle Eastern	36.8%	3
African / African-American	14.3%	7

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: ACBD5
Protein: p.Pro173=
Coding: c.519A>G
MANE Select: NM_145698
dbSNP: rs10764690
Type: single nucleotide variant
Location: chr10:27219829 (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 c.936+1G>A Likely pathogenic ★ same condition
ACBD5 c.1565+2T>A Uncertain significance ★ 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-p-pro173 (accessed [today's date]).

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