Is AMPD1 p.Leu607= (c.1819T>C) pathogenic?

AMPD1 p.Leu607= (c.1819T>C) is classified Conflicting classifications of pathogenicity in AMPD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-05). Ultra-rare (popmax 0.0906%, afr); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Leu607= (c.1819T>C)?

AMPD1 p.Leu607= (c.1819T>C) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Leu607= (c.1819T>C) in the general population?

AMPD1 p.Leu607= (c.1819T>C) is ultra-rare (popmax 0.0906%, afr) (gnomAD).

AMPD1 p.Leu607=

c.1819T>C · rs141900642 · VCV289235

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0906%, 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 0.69	GERP -2.4, phastCons 0.42
Overall
CADD	3.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0906% African / African-American · 68/75,060 alleles

Filtering AF 0.0733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.067%

Overall 0.00458% 74/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0906%	1,104
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.00017%	589,918

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.Leu607=
Coding: c.1819T>C
MANE Select: NM_000036
dbSNP: rs141900642
Type: single nucleotide variant
Location: chr1:114674064 (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-leu607 (accessed [today's date]).

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