Is AMPD2 p.Arg273Trp (c.817C>T) pathogenic?

AMPD2 p.Arg273Trp (c.817C>T) is classified Uncertain significance in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.2145); Ultra-rare (popmax 0.0147%, afr).

How common is AMPD2 p.Arg273Trp (c.817C>T) in the general population?

AMPD2 p.Arg273Trp (c.817C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about AMPD2 p.Arg273Trp (c.817C>T)?

AlphaMissense predicts likely benign (score 0.2145) — an in-silico prediction, not a clinical call.

AMPD2 p.Arg273Trp

c.817C>T · rs141742198 · VCV1809871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2145 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Computational evidence

Protein change
AlphaMissense	0.2145	likely benign
REVEL	0.414	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.8, phastCons 0.97
Regional constraint	o/e 0.89	unconstrained · MANE · 1,721 bp · p 0.065 · regional, not allelic
Overall
CADD	27.9	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 R327W vs ClinVar R273W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,808 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00218% 35/1,607,870 alleles · ultra-rare exomes 30/1,455,746 · genomes 5/152,124 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,801
Admixed American	0.0117%	8,511
European (non-Finnish)	0.00145%	69,203

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.Arg273Trp
Coding: c.817C>T
MANE Select: NM_001368809
dbSNP: rs141742198
Type: single nucleotide variant
Location: chr1:109627273 (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

Similar variants

AMPD2 p.Arg273Gln Uncertain significance ★ ⚠ same residue
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-arg273trp (accessed [today's date]).

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