Is AMPD3 p.Ala141= (c.423C>T) pathogenic?

AMPD3 p.Ala141= (c.423C>T) is classified Uncertain significance in AMPD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Low-frequency (popmax 2.82%, eas); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.Ala141= (c.423C>T)?

AMPD3 p.Ala141= (c.423C>T) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.Ala141= (c.423C>T) in the general population?

AMPD3 p.Ala141= (c.423C>T) is low-frequency (popmax 2.82%, eas) (gnomAD).

AMPD3 p.Ala141=

c.423C>T · rs117002871 · VCV302153

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.82%, eas)

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 -20	GERP -3.2
Overall
CADD	0.255	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.82% East Asian · 1,265/44,882 alleles

Filtering AF 2.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.0913% 1,471/1,611,514 alleles · low-frequency exomes 1,317/1,459,226 · genomes 154/152,288 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.82%	35
South Asian	0.142%	706
Remaining individualsnot grpmax-eligible	0.0864%	1,157
Middle Eastern	0.033%	3,026
Admixed American	0.00666%	15,006
African / African-American	0.00533%	18,757
European (non-Finnish)	0.0011%	90,770

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.Ala141=
Coding: c.423C>T
MANE Select: NM_001025389
dbSNP: rs117002871
Type: single nucleotide variant
Location: chr11:10478727 (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.Arg426Trp Uncertain significance ★★ ⚠ same condition
AMPD3 p.Arg576= Uncertain significance ★★ same condition
AMPD3 p.Asn279Ser 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-ala141 (accessed [today's date]).

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