Is AMPD2 p.Ala504= (c.1512C>T) pathogenic?

AMPD2 p.Ala504= (c.1512C>T) is classified Likely benign in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). Very rare (popmax 0.00112%, sas); Associated with pontocerebellar hypoplasia type 9.

What condition is associated with AMPD2 p.Ala504= (c.1512C>T)?

AMPD2 p.Ala504= (c.1512C>T) is associated with pontocerebellar hypoplasia type 9, hereditary spastic paraplegia 63 (ClinVar).

How common is AMPD2 p.Ala504= (c.1512C>T) in the general population?

AMPD2 p.Ala504= (c.1512C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

AMPD2 p.Ala504=

c.1512C>T · rs769002205 · VCV1594764

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, 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
Constraint at this position
Conservation	phyloP -14	GERP -4.2
Overall
CADD	4.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,304 alleles

Filtering AF 0.000294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000563% 9/1,598,532 alleles · very rare exomes 9/1,446,214 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,304
European (non-Finnish)	0.000683%	146,491

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.Ala504=
Coding: c.1512C>T
MANE Select: NM_001368809
dbSNP: rs769002205
Type: single nucleotide variant
Location: chr1:109628747 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 504: an α-helix

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-ala504 (accessed [today's date]).

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