Is APTX p.Met89Val (c.265A>G) pathogenic?

APTX p.Met89Val (c.265A>G) is classified Uncertain significance in APTX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). Very rare (popmax 0.0028%, nfe); Associated with Inborn genetic diseases.

What condition is associated with APTX p.Met89Val (c.265A>G)?

APTX p.Met89Val (c.265A>G) is associated with Inborn genetic diseases (ClinVar).

How common is APTX p.Met89Val (c.265A>G) in the general population?

APTX p.Met89Val (c.265A>G) is very rare (popmax 0.0028%, nfe) (gnomAD).

APTX p.Met89Val

c.265A>G · VCV3887133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.076	moderately benign-leaning
Splicing
SpliceAI	Δ0.34	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.6	GERP -0.86, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic
Overall
CADD	14.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0028% European (non-Finnish) · 33/1,180,034 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00253% 37/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,759
East Asian	0.00223%	44,890
Admixed American	0.00167%	60,032
African / African-American	0.00133%	75,066
South Asian	0.0011%	91,088

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.Met89Val
Coding: c.265A>G
MANE Select: NM_001195248
Type: single nucleotide variant
Location: chr9:32987762 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 89: the 'interactions with adprt/parp1 and ncl' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APTX p.Arg29His Uncertain significance ★★ same condition
APTX p.Arg3Gln Uncertain significance ★★ same condition
APTX p.Asn120Ser Uncertain significance ★★ same condition
APTX p.Glu103Lys Uncertain significance ★★ same condition
APTX p.Glu131Lys Uncertain significance ★★ same condition
APTX p.His320Leu Uncertain significance ★★ same condition
APTX p.Ile124Leu Uncertain significance ★★ same condition
APTX p.Ile17Phe 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-met89val (accessed [today's date]).

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