Is AMPD3 p.Ser482Leu (c.1445C>T) pathogenic?

AMPD3 p.Ser482Leu (c.1445C>T) is classified Uncertain significance in AMPD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-14). AlphaMissense: likely benign (0.0853); Rare (popmax 0.101%, nfe); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.Ser482Leu (c.1445C>T)?

AMPD3 p.Ser482Leu (c.1445C>T) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.Ser482Leu (c.1445C>T) in the general population?

AMPD3 p.Ser482Leu (c.1445C>T) is rare (popmax 0.101%, nfe) (gnomAD).

What do computational predictors say about AMPD3 p.Ser482Leu (c.1445C>T)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

AMPD3 p.Ser482Leu

c.1445C>T · rs144107914 · VCV193613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Erythrocyte AMP deaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -7.99	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 2.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	22.4	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 0.101% European (non-Finnish) · 1,187/1,180,026 alleles

Filtering AF 0.0958% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0938%

Overall 0.0783% 1,263/1,614,018 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.101%	994
Remaining individualsnot grpmax-eligible	0.0768%	1,302
Admixed American	0.03%	3,333
African / African-American	0.012%	8,322
South Asian	0.0011%	91,090

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.Ser482Leu
Coding: c.1445C>T
MANE Select: NM_001025389
dbSNP: rs144107914
Type: single nucleotide variant
Location: chr11:10496826 (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-ser482leu (accessed [today's date]).

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