Is AMPD1 p.Arg196Gln (c.587G>A) pathogenic?

AMPD1 p.Arg196Gln (c.587G>A) is classified Uncertain significance in AMPD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-28). AlphaMissense: likely benign (0.0721); Ultra-rare (popmax 0.0626%, sas); Associated with Inborn genetic diseases.

What condition is associated with AMPD1 p.Arg196Gln (c.587G>A)?

AMPD1 p.Arg196Gln (c.587G>A) is associated with Inborn genetic diseases, myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Arg196Gln (c.587G>A) in the general population?

AMPD1 p.Arg196Gln (c.587G>A) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

What do computational predictors say about AMPD1 p.Arg196Gln (c.587G>A)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

AMPD1 p.Arg196Gln

c.587G>A · rs149424604 · VCV2439023

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.111	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -2.8
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.9 · regional, not allelic
Overall
CADD	14.52	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R229Q vs ClinVar R196Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% South Asian · 57/91,062 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00564% 91/1,614,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Middle Eastern	0.0495%	2,019
African / African-American	0.00667%	15,004
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,868
European (non-Finnish)	0.00186%	53,638
Admixed American	0.00167%	60,008

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.Arg196Gln
Coding: c.587G>A
MANE Select: NM_000036
dbSNP: rs149424604
Type: single nucleotide variant
Location: chr1:114680439 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myopathy due to myoadenylate deaminase deficiency

Similar variants

AMPD1 p.Arg196Ter 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-arg196gln (accessed [today's date]).

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