Is AMPD3 p.Asn325Ser (c.974A>G) pathogenic?

AMPD3 p.Asn325Ser (c.974A>G) is classified Uncertain significance in AMPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1469); Rare (popmax 0.113%, nfe); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.Asn325Ser (c.974A>G)?

AMPD3 p.Asn325Ser (c.974A>G) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.Asn325Ser (c.974A>G) in the general population?

AMPD3 p.Asn325Ser (c.974A>G) is rare (popmax 0.113%, nfe) (gnomAD).

What do computational predictors say about AMPD3 p.Asn325Ser (c.974A>G)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

AMPD3 p.Asn325Ser

c.974A>G · rs147246880 · VCV880230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Erythrocyte AMP deaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.591	indeterminate
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	23.3	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 0.113% European (non-Finnish) · 1,334/1,180,024 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0938% 1,514/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.122%	821
European (non-Finnish)grpmax	0.113%	885
Remaining individualsnot grpmax-eligible	0.0704%	1,421
Middle Eastern	0.066%	1,516
Admixed American	0.0516%	1,936
South Asian	0.0176%	5,692
African / African-American	0.00933%	10,720

Finnish 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.Asn325Ser
Coding: c.974A>G
MANE Select: NM_001025389
dbSNP: rs147246880
Type: single nucleotide variant
Location: chr11:10493383 (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-p-asn325ser (accessed [today's date]).

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