Is AMPD2 p.Arg158Cys (c.472C>T) pathogenic?

AMPD2 p.Arg158Cys (c.472C>T) is classified Uncertain significance in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely benign (0.1633); Ultra-rare (popmax 0.0165%, sas); Associated with Inborn genetic diseases.

What condition is associated with AMPD2 p.Arg158Cys (c.472C>T)?

AMPD2 p.Arg158Cys (c.472C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AMPD2 p.Arg158Cys (c.472C>T) in the general population?

AMPD2 p.Arg158Cys (c.472C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about AMPD2 p.Arg158Cys (c.472C>T)?

AlphaMissense predicts likely benign (score 0.1633) — an in-silico prediction, not a clinical call.

AMPD2 p.Arg158Cys

c.472C>T · VCV4576477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1633 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1633	likely benign
REVEL	0.498	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,721 bp · p 0.065 · regional, not allelic
Overall
CADD	26.3	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 R212C vs ClinVar R158C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/90,958 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00105% 17/1,612,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,064
Remaining individualsnot grpmax-eligible	0.0016%	62,358
European (non-Finnish)	8.48e-05%	1,179,244

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.Arg158Cys
Coding: c.472C>T
MANE Select: NM_001368809
Type: single nucleotide variant
Location: chr1:109626368 (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.Arg158= Likely benign ★ 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
AMPD2 p.Asn746Ser 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-arg158cys (accessed [today's date]).

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