Is AMPD1 p.Phe41fs (c.122_137del) pathogenic?

AMPD1 p.Phe41fs (c.122137del) is classified Likely pathogenic in AMPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). Very rare (popmax 0.00133%, afr); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Phe41fs (c.122_137del)?

AMPD1 p.Phe41fs (c.122_137del) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Phe41fs (c.122_137del) in the general population?

AMPD1 p.Phe41fs (c.122_137del) is very rare (popmax 0.00133%, afr) (gnomAD).

AMPD1 p.Phe41fs

c.122_137del · VCV4850256

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 3 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP -1.1, phastCons 1
Overall
CADD	33.0	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 0.00133% African / African-American · 1/74,916 alleles

Overall 6.2e-05% 1/1,614,066 alleles · very rare exomes 0/1,461,882 · genomes 1/152,184 · joint denominator

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.Phe41fs
Coding: c.122_137del
MANE Select: NM_000036
Type: Deletion
Location: chr1:114688639 (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 c.382-6del Benign/Likely benign ★★ 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
AMPD1 p.Ile135fs Uncertain significance ★ same condition
AMPD1 p.Leu387fs 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-phe41fs (accessed [today's date]).

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