Is AMPD3 p.Asp95Asn (c.283G>A) pathogenic?

AMPD3 p.Asp95Asn (c.283G>A) is classified Uncertain significance in AMPD3 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1067); Very rare (popmax 0.00915%, nfe); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.Asp95Asn (c.283G>A)?

AMPD3 p.Asp95Asn (c.283G>A) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.Asp95Asn (c.283G>A) in the general population?

AMPD3 p.Asp95Asn (c.283G>A) is very rare (popmax 0.00915%, nfe) (gnomAD).

What do computational predictors say about AMPD3 p.Asp95Asn (c.283G>A)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

AMPD3 p.Asp95Asn

c.283G>A · rs149433198 · VCV302148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00915%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Erythrocyte AMP deaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00915% European (non-Finnish) · 108/1,180,050 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.0515% 831/1,614,084 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.12%	47
Remaining individualsnot grpmax-eligible	0.152%	658
European (non-Finnish)grpmax	0.00915%	10,926
African / African-American	0.00133%	74,926

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Protein: p.Asp95Asn
Coding: c.283G>A
MANE Select: NM_001025389
dbSNP: rs149433198
Type: single nucleotide variant
Location: chr11:10478587 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74
Residue 95: the 'disordered' region

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-p-asp95asn (accessed [today's date]).

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