Is AMPD1 p.Phe184= (c.552T>C) pathogenic?

AMPD1 p.Phe184= (c.552T>C) is classified Benign in AMPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). Low-frequency (popmax 2.19%, afr); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Phe184= (c.552T>C)?

AMPD1 p.Phe184= (c.552T>C) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Phe184= (c.552T>C) in the general population?

AMPD1 p.Phe184= (c.552T>C) is low-frequency (popmax 2.19%, afr) (gnomAD).

AMPD1 p.Phe184=

c.552T>C · rs35197706 · VCV529205

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.19%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -1.2, phastCons 1
Overall
CADD	8.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.19% African / African-American · 1,642/75,016 alleles

Filtering AF 2.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.07%

Overall 0.114% 1,833/1,614,016 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.19%	46
Remaining individualsnot grpmax-eligible	0.146%	687
Admixed American	0.137%	732
Middle Eastern	0.033%	3,031
East Asian	0.00669%	14,957
South Asian	0.00329%	30,359
European (non-Finnish)	0.000848%	117,993

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.Phe184=
Coding: c.552T>C
MANE Select: NM_000036
dbSNP: rs35197706
Type: single nucleotide variant
Location: chr1:114680474 (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-phe184 (accessed [today's date]).

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