Is AMPD1 p.Arg263His (c.788G>A) pathogenic?

AMPD1 p.Arg263His (c.788G>A) is classified Uncertain significance in AMPD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-06-21). AlphaMissense: likely pathogenic (0.7985); Very rare (popmax 0.00559%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMPD1 p.Arg263His (c.788G>A)?

AMPD1 p.Arg263His (c.788G>A) is associated with Inborn genetic diseases, myopathy due to myoadenylate deaminase deficiency (ClinVar).

How common is AMPD1 p.Arg263His (c.788G>A) in the general population?

AMPD1 p.Arg263His (c.788G>A) is very rare (popmax 0.00559%, nfe) (gnomAD).

What do computational predictors say about AMPD1 p.Arg263His (c.788G>A)?

AlphaMissense predicts likely pathogenic (score 0.7985) — an in-silico prediction, not a clinical call.

AMPD1 p.Arg263His

c.788G>A · rs775559099 · VCV2068373

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7985	likely pathogenic
REVEL	0.919	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.9 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 R296H vs ClinVar R263H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00559% European (non-Finnish) · 66/1,179,970 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00415% 67/1,613,742 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00559%	17,878
African / African-American	0.00134%	74,828

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.Arg263His
Coding: c.788G>A
MANE Select: NM_000036
dbSNP: rs775559099
Type: single nucleotide variant
Location: chr1:114679688 (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.Arg263Cys 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-arg263his (accessed [today's date]).

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