Is AMPD3 c.-116A>C pathogenic?

AMPD3 c.-116A>C is classified Uncertain significance in AMPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00337%, nfe); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 c.-116A>C?

AMPD3 c.-116A>C is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 c.-116A>C in the general population?

AMPD3 c.-116A>C is very rare (popmax 0.00337%, nfe) (gnomAD).

AMPD3 c.-116A>C

rs891567072 · VCV878960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00337%, nfe)

Conditions

Erythrocyte AMP deaminase deficiency

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 0.38	GERP -0.42, phastCons 0.11
Non-coding constraint	Z 2.34	1 kb window · o/e 0.83 · regional · uncalibrated
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00337% European (non-Finnish) · 28/829,998 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00201%

Overall 0.00294% 29/985,298 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00337%	29,643
African / African-American	0.00175%	57,202

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: AMPD3
Coding: c.-116A>C
MANE Select: NM_001025389
dbSNP: rs891567072
Type: single nucleotide variant
Location: chr11:10455338 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74

Full AMPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Erythrocyte AMP deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMPD3 c.1135-5C>A Uncertain significance ★★ same condition
AMPD3 c.1135-6C>G Uncertain significance ★★ same condition
AMPD3 c.1267-3C>T Uncertain significance ★★ same condition
AMPD3 c.*287T>C Uncertain significance ★★ same condition
AMPD3 c.*75C>T Uncertain significance ★★ same condition
AMPD3 p.Ala141= Uncertain significance ★★ same condition
AMPD3 p.Arg426Trp Uncertain significance ★★ ⚠ same condition
AMPD3 p.Arg576= 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/ampd3-c-minus-116a-c (accessed [today's date]).

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