Is APTX p.Leu171= (c.513G>A) pathogenic?

APTX p.Leu171= (c.513G>A) is classified Conflicting classifications of pathogenicity in APTX (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-08-16). Ultra-rare (popmax 0.0837%, nfe); Associated with ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia.

What condition is associated with APTX p.Leu171= (c.513G>A)?

APTX p.Leu171= (c.513G>A) is associated with ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (ClinVar).

How common is APTX p.Leu171= (c.513G>A) in the general population?

APTX p.Leu171= (c.513G>A) is ultra-rare (popmax 0.0837%, nfe) (gnomAD).

How is Ataxia-oculomotor apraxia type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

APTX p.Leu171=

c.513G>A · rs140888559 · VCV262911

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0837%, nfe)

Conditions

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia

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 1.8	GERP -0.29, phastCons 1
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0837% European (non-Finnish) · 926/1,106,886 alleles

Filtering AF 0.0792% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0774%

Overall 0.0668% 994/1,489,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0837%	1,195
Remaining individualsnot grpmax-eligible	0.0679%	1,474
Admixed American	0.0318%	3,149
African / African-American	0.0191%	5,226
South Asian	0.00113%	88,308

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: APTX
Protein: p.Leu171=
Coding: c.513G>A
MANE Select: NM_001195248
dbSNP: rs140888559
Type: single nucleotide variant
Location: chr9:32986001 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB

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

Disease context

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ataxia-oculomotor apraxia type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

APTX c.875-2A>G Pathogenic/Likely pathogenic ★★ same condition
APTX p.Ala198Val Likely pathogenic ★★ same condition
APTX p.Arg16Ter Pathogenic/Likely pathogenic ★★ same condition
APTX p.Gln130Ter Pathogenic/Likely pathogenic ★★ same condition
APTX p.Trp279Ter Pathogenic ★★ same condition
APTX p.Arg247Gln Uncertain significance ★★ same condition
APTX p.Glu125Asp Uncertain significance ★★ same condition
APTX p.His166Tyr 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/aptx-p-leu171 (accessed [today's date]).

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