Is AMPD1 p.Asp649= (c.1947T>C) pathogenic?

AMPD1 p.Asp649= (c.1947T>C) is classified Benign in AMPD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.77%, afr); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Asp649= (c.1947T>C)?

AMPD1 p.Asp649= (c.1947T>C) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Asp649= (c.1947T>C) in the general population?

AMPD1 p.Asp649= (c.1947T>C) is low-frequency (popmax 1.77%, afr) (gnomAD).

AMPD1 p.Asp649=

c.1947T>C · rs34287100 · VCV92334

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.77%, 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 -0.35	GERP -1.3
Overall
CADD	4.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.77% African / African-American · 1,329/75,044 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.66%

Overall 0.0964% 1,556/1,614,134 alleles · low-frequency exomes 768/1,461,828 · genomes 788/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.77%	56
Remaining individualsnot grpmax-eligible	0.15%	665
Admixed American	0.145%	690
Middle Eastern	0.115%	866
South Asian	0.00439%	22,771
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00288%	34,706

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.Asp649=
Coding: c.1947T>C
MANE Select: NM_000036
dbSNP: rs34287100
Type: single nucleotide variant
Location: chr1:114673936 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.84
Residue 649: a binding site

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.Asp649Gly Uncertain significance ★ ⚠ same residue
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

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-asp649 (accessed [today's date]).

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