Is AMPD2 p.Arg324Pro (c.971G>C) pathogenic?

AMPD2 p.Arg324Pro (c.971G>C) is classified Likely pathogenic in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2013-11-21). AlphaMissense: likely pathogenic (0.9993); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMPD2 p.Arg324Pro (c.971G>C)?

AMPD2 p.Arg324Pro (c.971G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AMPD2 p.Arg324Pro (c.971G>C) in the general population?

AMPD2 p.Arg324Pro (c.971G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AMPD2 p.Arg324Pro (c.971G>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

AMPD2 p.Arg324Pro

c.971G>C · rs746332433 · VCV224991

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in AMPD2
REVEL	0.956	strongly pathogenic-leaning
SaProt	—	withheld · numbering disagrees past residue 5 · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.23	acceptor gain, 8 bp away · raw score · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 625 bp · p 2.1e-07 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R378P vs ClinVar R324P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,970 alleles

Overall 6.2e-05% 1/1,613,948 alleles · very rare exomes 1/1,461,828 · genomes 0/152,120 · joint denominator

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: AMPD2
Protein: p.Arg324Pro
Coding: c.971G>C
MANE Select: NM_001368809
dbSNP: rs746332433
Type: single nucleotide variant
Location: chr1:109627794 (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

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

Similar variants

AMPD2 p.Arg324Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
AMPD2 p.Arg324Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
AMPD2 c.-150G>A Uncertain significance ★★ ⚠ same condition
AMPD2 c.-18G>T Uncertain significance ★★ ⚠ same condition
AMPD2 p.Ala425= Uncertain significance ★★ same condition
AMPD2 p.Arg156Gln Uncertain significance ★★ ⚠ same condition
AMPD2 p.Arg163Gln Uncertain significance ★★ ⚠ same condition
AMPD2 p.Arg386Trp 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/ampd2-p-arg324pro (accessed [today's date]).

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