Is AMPD2 p.Ala798Val (c.2393C>T) pathogenic?

AMPD2 p.Ala798Val (c.2393C>T) is classified Uncertain significance in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1186); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with AMPD2 p.Ala798Val (c.2393C>T)?

AMPD2 p.Ala798Val (c.2393C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AMPD2 p.Ala798Val (c.2393C>T) in the general population?

AMPD2 p.Ala798Val (c.2393C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about AMPD2 p.Ala798Val (c.2393C>T)?

AlphaMissense predicts likely benign (score 0.1186) — an in-silico prediction, not a clinical call.

AMPD2 p.Ala798Val

c.2393C>T · VCV4576507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1186	likely benign
REVEL	0.249	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,009 bp · p 8.7e-13 · regional, not allelic
Overall
CADD	23.2	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 A852V vs ClinVar A798V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,956 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,606 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,978
European (non-Finnish)	0.000424%	235,966

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.Ala798Val
Coding: c.2393C>T
MANE Select: NM_001368809
Type: single nucleotide variant
Location: chr1:109631067 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 798: an α-helix

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 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
AMPD2 p.Asn746Ser Uncertain significance ★★ ⚠ same condition
AMPD2 p.Asp60Asn 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-ala798val (accessed [today's date]).

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