Is AMPD1 p.Leu688Phe (c.2064G>T) pathogenic?

AMPD1 p.Leu688Phe (c.2064G>T) is classified Uncertain significance in AMPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). AlphaMissense: likely benign (0.22); Absent from gnomAD v4.1; Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Leu688Phe (c.2064G>T)?

AMPD1 p.Leu688Phe (c.2064G>T) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Leu688Phe (c.2064G>T) in the general population?

AMPD1 p.Leu688Phe (c.2064G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMPD1 p.Leu688Phe (c.2064G>T)?

AlphaMissense predicts likely benign (score 0.22) — an in-silico prediction, not a clinical call.

AMPD1 p.Leu688Phe

c.2064G>T · VCV4743456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.22 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

myopathy due to myoadenylate deaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.22	likely benign
REVEL	0.734	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 0.64, phastCons 0.97
Regional constraint	o/e 0.71	unconstrained · MANE · 862 bp · p 0.00064 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L721F vs ClinVar L688F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMPD1
Protein: p.Leu688Phe
Coding: c.2064G>T
MANE Select: NM_000036
Type: single nucleotide variant
Location: chr1:114673660 (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.Leu688Ser 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-leu688phe (accessed [today's date]).

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