Is AMPD3 p.His608= (c.1824C>T) pathogenic?

AMPD3 p.His608= (c.1824C>T) is classified Conflicting classifications of pathogenicity in AMPD3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-03). Ultra-rare (popmax 0.0357%, eas); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.His608= (c.1824C>T)?

AMPD3 p.His608= (c.1824C>T) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.His608= (c.1824C>T) in the general population?

AMPD3 p.His608= (c.1824C>T) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

AMPD3 p.His608=

c.1824C>T · rs201980416 · VCV194013

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, 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 -4.8
Overall
CADD	0.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% East Asian · 16/44,878 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00613% 99/1,614,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,805
European (non-Finnish)	0.00669%	14,937
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,028
South Asian	0.0011%	91,080

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.His608=
Coding: c.1824C>T
MANE Select: NM_001025389
dbSNP: rs201980416
Type: single nucleotide variant
Location: chr11:10501572 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74
Residue 608: an active site

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-his608 (accessed [today's date]).

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