Is AMPD3 p.Arg573His (c.1718G>A) pathogenic?

AMPD3 p.Arg573His (c.1718G>A) is classified Uncertain significance in AMPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-14). AlphaMissense: likely pathogenic (0.903); Very rare (popmax 0.004%, afr).

How common is AMPD3 p.Arg573His (c.1718G>A) in the general population?

AMPD3 p.Arg573His (c.1718G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about AMPD3 p.Arg573His (c.1718G>A)?

AlphaMissense predicts likely pathogenic (score 0.903) — an in-silico prediction, not a clinical call.

AMPD3 p.Arg573His

c.1718G>A · rs771210624 · VCV2560222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.903	likely pathogenic
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.004% African / African-American · 3/74,916 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00235% 38/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,972
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,888
South Asian	0.0022%	45,540

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.Arg573His
Coding: c.1718G>A
MANE Select: NM_001025389
dbSNP: rs771210624
Type: single nucleotide variant
Location: chr11:10500246 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74
Residue 573: a UniProt-annotated variant site (in ampdde; enzyme inactive)

Full AMPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMPD3 p.Arg573Cys Pathogenic ★ same residue
AMPD3 c.1135-5C>A Uncertain significance ★★ same type
AMPD3 c.1135-6C>G Uncertain significance ★★ same type
AMPD3 c.1267-3C>T Uncertain significance ★★ same type
AMPD3 c.*287T>C Uncertain significance ★★ same type
AMPD3 c.*75C>T Uncertain significance ★★ same type
AMPD3 p.Ala141= Uncertain significance ★★ same type
AMPD3 p.Arg426Trp Uncertain significance ★★ ⚠ same type

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-arg573his (accessed [today's date]).

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