Is AMPD2 p.Glu724Asp (c.2172G>C) pathogenic?

AMPD2 p.Glu724Asp (c.2172G>C) is classified Pathogenic in AMPD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-23). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with pontocerebellar hypoplasia.

What condition is associated with AMPD2 p.Glu724Asp (c.2172G>C)?

AMPD2 p.Glu724Asp (c.2172G>C) is associated with pontocerebellar hypoplasia, pontocerebellar hypoplasia type 9 (ClinVar).

How common is AMPD2 p.Glu724Asp (c.2172G>C) in the general population?

AMPD2 p.Glu724Asp (c.2172G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMPD2 p.Glu724Asp (c.2172G>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

AMPD2 p.Glu724Asp

c.2172G>C · rs587777392 · VCV132810

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

pontocerebellar hypoplasia

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 1% in AMPD2
REVEL	0.75	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.81	GERP -1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,009 bp · p 8.7e-13 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E778D vs ClinVar E724D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMPD2
Protein: p.Glu724Asp
Coding: c.2172G>C
MANE Select: NM_001368809
dbSNP: rs587777392
Type: single nucleotide variant
Location: chr1:109630697 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 724: a UniProt-annotated variant site (in pch9); an α-helix

Full AMPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pontocerebellar hypoplasia type 9

Similar variants

AMPD2 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg449Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg620His Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg789His Likely pathogenic ★★ same condition
AMPD2 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD2 c.1080+3G>A Uncertain significance ★★ same condition
AMPD2 c.353+3G>A 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/ampd2-p-glu724asp (accessed [today's date]).

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