Is APTX p.Lys197fs (c.588_595del) pathogenic?

APTX p.Lys197fs (c.588595del) is classified Pathogenic in APTX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). Very rare (popmax 0.00134%, afr).

How common is APTX p.Lys197fs (c.588_595del) in the general population?

APTX p.Lys197fs (c.588_595del) is very rare (popmax 0.00134%, afr) (gnomAD).

APTX p.Lys197fs

c.588_595del · rs1563961179 · VCV2019865

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 0.8, phastCons 1
Overall
CADD	35.0	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

Grpmax group 0.00134% African / African-American · 1/74,906 alleles

Overall 0.000657% 1/152,158 alleles · very 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: APTX
Protein: p.Lys197fs
Coding: c.588_595del
MANE Select: NM_001195248
dbSNP: rs1563961179
Type: Deletion
Location: chr9:32984806 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 197: the hit domain; a β-strand

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

Similar variants

APTX p.Arg199fs Pathogenic/Likely pathogenic ★★ same type
APTX p.Val259fs Pathogenic ★★ same type
APTX c.484-13del Likely benign ★★ same type
APTX c.484-15_484-3del Benign/Likely benign ★★ same type
APTX c.484-25_484-3del Likely benign ★★ same type
APTX c.484-25_484-4del Benign ★★ same type
APTX c.484-25_484-5del Benign/Likely benign ★★ same type
APTX c.484-25_484-6del Benign ★★ same type

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-lys197fs (accessed [today's date]).

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