Is AMPD2 p.Cys288= (c.864C>T) pathogenic?

AMPD2 p.Cys288= (c.864C>T) is classified Likely benign in AMPD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-20). Very rare (popmax 0.005%, amr); Associated with AMPD2-related disorder.

What condition is associated with AMPD2 p.Cys288= (c.864C>T)?

AMPD2 p.Cys288= (c.864C>T) is associated with AMPD2-related disorder (ClinVar).

How common is AMPD2 p.Cys288= (c.864C>T) in the general population?

AMPD2 p.Cys288= (c.864C>T) is very rare (popmax 0.005%, amr) (gnomAD).

AMPD2 p.Cys288=

c.864C>T · rs777653877 · VCV3052064

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

AMPD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2.1, phastCons 0.89
Overall
CADD	11.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00161% 26/1,613,974 alleles · very rare exomes 23/1,461,832 · genomes 3/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
European (non-Finnish)	0.00195%	51,304

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.Cys288=
Coding: c.864C>T
MANE Select: NM_001368809
dbSNP: rs777653877
Type: single nucleotide variant
Location: chr1:109627432 (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

AMPD2-related disorder

Similar variants

AMPD2 p.Glu450Ter Pathogenic ★ same condition
AMPD2 p.Glu92Ter Likely pathogenic ★ same condition
AMPD2 c.1633G>A Uncertain significance ★ same condition
AMPD2 c.2138T>C Uncertain significance ★ same condition
AMPD2 c.743T>C Uncertain significance ★ same condition
AMPD2 p.Glu343= Likely benign same condition
AMPD2 p.Leu421= Likely benign same condition
AMPD2 c.1698+1G>A Pathogenic/Likely pathogenic ★★ 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/ampd2-p-cys288 (accessed [today's date]).

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