Is AMPD1 p.Val444Ile (c.1330G>A) pathogenic?

AMPD1 p.Val444Ile (c.1330G>A) is classified Uncertain significance in AMPD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-07). AlphaMissense: likely benign (0.0794); Very rare (popmax 0.0067%, eas); Associated with myopathy due to myoadenylate deaminase deficiency.

What condition is associated with AMPD1 p.Val444Ile (c.1330G>A)?

AMPD1 p.Val444Ile (c.1330G>A) is associated with myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Val444Ile (c.1330G>A) in the general population?

AMPD1 p.Val444Ile (c.1330G>A) is very rare (popmax 0.0067%, eas) (gnomAD).

What do computational predictors say about AMPD1 p.Val444Ile (c.1330G>A)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

AMPD1 p.Val444Ile

c.1330G>A · rs760431058 · VCV2046342

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Conditions

myopathy due to myoadenylate deaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.329	indeterminate
Splicing
SpliceAI	Δ0.21	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.9 · regional, not allelic
Overall
CADD	17.1	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 V477I vs ClinVar V444I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,802 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00186% 30/1,611,468 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,934
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
South Asian	0.0022%	45,443
European (non-Finnish)	0.00195%	51,287
Remaining individualsnot grpmax-eligible	0.0016%	62,420

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.Val444Ile
Coding: c.1330G>A
MANE Select: NM_000036
dbSNP: rs760431058
Type: single nucleotide variant
Location: chr1:114677409 (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.Val444Asp 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-val444ile (accessed [today's date]).

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