Is APTX p.Gln187Ter (c.559C>T) pathogenic?

APTX p.Gln187Ter (c.559C>T) is classified Pathogenic in APTX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-16). Very rare (popmax 0.000509%, nfe).

How common is APTX p.Gln187Ter (c.559C>T) in the general population?

APTX p.Gln187Ter (c.559C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

APTX p.Gln187Ter

c.559C>T · rs770579215 · VCV870837

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	Δ0.31	acceptor loss · deltas
Pangolin	Δ0.24	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.4	GERP 0.87, phastCons 1
Overall
CADD	43.0	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 0.000509% European (non-Finnish) · 6/1,179,932 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,950 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.Gln187Ter
Coding: c.559C>T
MANE Select: NM_001195248
dbSNP: rs770579215
Type: single nucleotide variant
Location: chr9:32984842 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 187: the hit domain; an α-helix

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

Similar variants

APTX c.875-2A>G Pathogenic/Likely pathogenic ★★ same type
APTX p.Ala198Val Likely pathogenic ★★ same type
APTX p.Arg16Ter Pathogenic/Likely pathogenic ★★ same type
APTX p.Arg247Ter Pathogenic/Likely pathogenic ★★ same type
APTX p.Gln130Ter Pathogenic/Likely pathogenic ★★ same type
APTX p.Trp279Arg Pathogenic/Likely pathogenic ★★ same type
APTX p.Trp279Ter Pathogenic ★★ same type
APTX c.875-3C>T Uncertain significance ★★ 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-gln187ter (accessed [today's date]).

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