Is AMPD2 p.Ala816= (c.2448G>A) pathogenic?

AMPD2 p.Ala816= (c.2448G>A) is classified Likely benign in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). Ultra-rare (popmax 0.018%, sas); Associated with pontocerebellar hypoplasia type 9.

What condition is associated with AMPD2 p.Ala816= (c.2448G>A)?

AMPD2 p.Ala816= (c.2448G>A) is associated with pontocerebellar hypoplasia type 9, hereditary spastic paraplegia 63 (ClinVar).

How common is AMPD2 p.Ala816= (c.2448G>A) in the general population?

AMPD2 p.Ala816= (c.2448G>A) is ultra-rare (popmax 0.018%, sas) (gnomAD).

AMPD2 p.Ala816=

c.2448G>A · VCV3758500

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, sas)

Conditions

pontocerebellar hypoplasia type 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.53	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -2.5	GERP -1.2
Overall
CADD	2.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% South Asian · 16/88,694 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00921%

Overall 0.00351% 56/1,597,444 alleles · ultra-rare exomes 56/1,445,090 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.018%	5,543
European (non-Finnish)	0.00333%	30,061
Remaining individualsnot grpmax-eligible	0.00161%	61,942

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: AMPD2
Protein: p.Ala816=
Coding: c.2448G>A
MANE Select: NM_001368809
Type: single nucleotide variant
Location: chr1:109631122 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB

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

Disease context

pontocerebellar hypoplasia type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 63

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-ala816 (accessed [today's date]).

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