Is AMPD2 p.Ser572= (c.1716C>T) pathogenic?

AMPD2 p.Ser572= (c.1716C>T) is classified Benign/Likely benign in AMPD2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.05%, afr); Associated with pontocerebellar hypoplasia type 9.

What condition is associated with AMPD2 p.Ser572= (c.1716C>T)?

AMPD2 p.Ser572= (c.1716C>T) is associated with pontocerebellar hypoplasia type 9, hereditary spastic paraplegia 63 (ClinVar).

How common is AMPD2 p.Ser572= (c.1716C>T) in the general population?

AMPD2 p.Ser572= (c.1716C>T) is low-frequency (popmax 1.05%, afr) (gnomAD).

AMPD2 p.Ser572=

c.1716C>T · rs116415979 · VCV704004

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.05%, afr)

Conditions

pontocerebellar hypoplasia type 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.516	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.2	GERP -3.9
Overall
CADD	6.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.05% African / African-American · 786/75,028 alleles

Filtering AF 0.987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.963%

Overall 0.0758% 1,223/1,614,112 alleles · low-frequency exomes 776/1,461,838 · genomes 447/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.05%	95
Middle Eastern	0.33%	303
Remaining individualsnot grpmax-eligible	0.102%	977
South Asian	0.0889%	1,124
Admixed American	0.0666%	1,500
European (non-Finnish)	0.0196%	5,108
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Ser572=
Coding: c.1716C>T
MANE Select: NM_001368809
dbSNP: rs116415979
Type: single nucleotide variant
Location: chr1:109629344 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 572: a β-strand

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-ser572 (accessed [today's date]).

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