Is AMPD1 p.Pro2fs (c.5del) pathogenic?

AMPD1 p.Pro2fs (c.5del) is classified Conflicting classifications of pathogenicity in AMPD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.778%, sas); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Pro2fs (c.5del)?

AMPD1 p.Pro2fs (c.5del) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Pro2fs (c.5del) in the general population?

AMPD1 p.Pro2fs (c.5del) is rare (popmax 0.778%, sas) (gnomAD).

AMPD1 p.Pro2fs

c.5del · rs557878856 · VCV779692

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.778%, sas)

Conditions

myopathy due to myoadenylate deaminase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 0.92, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.778% South Asian · 709/91,076 alleles

Filtering AF 0.731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.712%

Overall 0.0457% 738/1,613,870 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.778%	128
Remaining individualsnot grpmax-eligible	0.032%	3,125
European (non-Finnish)	0.000763%	131,110

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: AMPD1
Protein: p.Pro2fs
Coding: c.5del
MANE Select: NM_000036
dbSNP: rs557878856
Type: Deletion
Location: chr1:114695467 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.84

Full AMPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myopathy due to myoadenylate deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMPD1 p.Pro2Ser Uncertain significance ★ ⚠ same residue
AMPD1 c.382-6del Benign/Likely benign ★★ same condition
AMPD1 p.Phe41fs Likely pathogenic ★ same condition
AMPD1 c.216-2del Uncertain significance ★ same condition
AMPD1 c.35-7_35-4del Conflicting classifications of pathogenicity ★ same condition
AMPD1 c.548-3_548-2del Uncertain significance ★ same condition
AMPD1 c.767+3_767+6del Uncertain significance ★ same condition
AMPD1 p.Gly78fs 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/ampd1-p-pro2fs (accessed [today's date]).

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