Is AMPD2 p.Gln146Arg (c.437A>G) pathogenic?

AMPD2 p.Gln146Arg (c.437A>G) is classified Likely benign in AMPD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0748); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with AMPD2 p.Gln146Arg (c.437A>G)?

AMPD2 p.Gln146Arg (c.437A>G) is associated with intellectual disability (ClinVar).

How common is AMPD2 p.Gln146Arg (c.437A>G) in the general population?

AMPD2 p.Gln146Arg (c.437A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMPD2 p.Gln146Arg (c.437A>G)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

AMPD2 p.Gln146Arg

c.437A>G · rs1650680448 · VCV975490

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.127	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 7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,721 bp · p 0.065 · regional, not allelic
Overall
CADD	23.0	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 Q200R vs ClinVar Q146R) — 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: AMPD2
Protein: p.Gln146Arg
Coding: c.437A>G
MANE Select: NM_001368809
dbSNP: rs1650680448
Type: single nucleotide variant
Location: chr1:109626333 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB

Full AMPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMPD2 p.Ser3Phe Uncertain significance ★★ same condition
AMPD2 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same type
AMPD2 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same type
AMPD2 p.Arg449Ter Pathogenic/Likely pathogenic ★★ same type
AMPD2 p.Arg620His Pathogenic/Likely pathogenic ★★ same type
AMPD2 p.Arg789His Likely pathogenic ★★ same type
AMPD2 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same type
AMPD2 c.1080+3G>A Uncertain significance ★★ same type

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/ampd2-p-gln146arg (accessed [today's date]).

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