Is AMPD3 p.Glu149Gln (c.445G>C) pathogenic?

AMPD3 p.Glu149Gln (c.445G>C) is classified Uncertain significance in AMPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.1188); Absent from gnomAD v4.1.

How common is AMPD3 p.Glu149Gln (c.445G>C) in the general population?

AMPD3 p.Glu149Gln (c.445G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMPD3 p.Glu149Gln (c.445G>C)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

AMPD3 p.Glu149Gln

c.445G>C · VCV4093145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	25.1	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.

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: AMPD3
Protein: p.Glu149Gln
Coding: c.445G>C
MANE Select: NM_001025389
Type: single nucleotide variant
Location: chr11:10482081 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74

Full AMPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMPD3 c.1135-5C>A Uncertain significance ★★ same type
AMPD3 c.1135-6C>G Uncertain significance ★★ same type
AMPD3 c.1267-3C>T Uncertain significance ★★ same type
AMPD3 c.*287T>C Uncertain significance ★★ same type
AMPD3 c.*75C>T Uncertain significance ★★ same type
AMPD3 p.Ala141= Uncertain significance ★★ same type
AMPD3 p.Arg426Trp Uncertain significance ★★ ⚠ same type
AMPD3 p.Arg576= 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/ampd3-p-glu149gln (accessed [today's date]).

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