Is APTX p.Val72Ile (c.214G>A) pathogenic?

APTX p.Val72Ile (c.214G>A) is classified Conflicting classifications of pathogenicity in APTX (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-15). Very rare (popmax 0.0039%, nfe); Associated with Inborn genetic diseases.

What condition is associated with APTX p.Val72Ile (c.214G>A)?

APTX p.Val72Ile (c.214G>A) is associated with Inborn genetic diseases (ClinVar).

How common is APTX p.Val72Ile (c.214G>A) in the general population?

APTX p.Val72Ile (c.214G>A) is very rare (popmax 0.0039%, nfe) (gnomAD).

APTX p.Val72Ile

c.214G>A · rs367998288 · VCV1427929

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.057	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -3.3, phastCons 0.4
Regional constraint	o/e 1.01	unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic
Overall
CADD	11.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% European (non-Finnish) · 46/1,180,040 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.0031% 50/1,613,746 alleles · very rare exomes 43/1,461,554 · genomes 7/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,653
Finnishnot grpmax-eligible	0.00312%	32,010
Remaining individualsnot grpmax-eligible	0.0016%	62,458
African / African-American	0.00133%	74,922

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.Val72Ile
Coding: c.214G>A
MANE Select: NM_001195248
dbSNP: rs367998288
Type: single nucleotide variant
Location: chr9:32987813 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 72: the fha-like domain; the 'interactions with adprt/parp1 and ncl' region; a β-strand

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-val72ile (accessed [today's date]).

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