Is AMPD1 p.Pro229= (c.687T>C) pathogenic?

AMPD1 p.Pro229= (c.687T>C) is classified Likely benign in AMPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-23). Very rare (popmax 0.000508%, nfe); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Pro229= (c.687T>C)?

AMPD1 p.Pro229= (c.687T>C) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Pro229= (c.687T>C) in the general population?

AMPD1 p.Pro229= (c.687T>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

AMPD1 p.Pro229=

c.687T>C · rs748174102 · VCV1536220

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

myopathy due to myoadenylate deaminase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.72	GERP -5.2
Overall
CADD	2.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,046 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,878 alleles · very rare

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.Pro229=
Coding: c.687T>C
MANE Select: NM_000036
dbSNP: rs748174102
Type: single nucleotide variant
Location: chr1:114680339 (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.Gln653Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD1 c.1388+5G>A Uncertain significance ★★ same condition
AMPD1 c.1974+1G>A Uncertain significance ★★ same condition
AMPD1 c.-42C>T Uncertain significance ★★ ⚠ same condition
AMPD1 p.Ala308Thr Uncertain significance ★★ ⚠ same condition
AMPD1 p.Ala489Thr Uncertain significance ★★ ⚠ same condition
AMPD1 p.Ala578Thr Uncertain significance ★★ ⚠ same condition
AMPD1 p.Ala616Thr 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-pro229 (accessed [today's date]).

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