Is AMPD2 p.Pro694= (c.2082G>A) pathogenic?

AMPD2 p.Pro694= (c.2082G>A) is classified Benign in AMPD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-11-27). Very rare (popmax 0.00754%, nfe).

How common is AMPD2 p.Pro694= (c.2082G>A) in the general population?

AMPD2 p.Pro694= (c.2082G>A) is very rare (popmax 0.00754%, nfe) (gnomAD).

AMPD2 p.Pro694=

c.2082G>A · rs201580843 · VCV789422

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00754%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.163	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -4.2
Overall
CADD	3.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00754% European (non-Finnish) · 89/1,180,016 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.0621% 1,003/1,613,988 alleles · very rare exomes 858/1,461,804 · genomes 145/152,184 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.37%	73
Remaining individualsnot grpmax-eligible	0.0576%	1,736
European (non-Finnish)grpmax	0.00754%	13,259
South Asian	0.0011%	91,080

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro694=
Coding: c.2082G>A
MANE Select: NM_001368809
dbSNP: rs201580843
Type: single nucleotide variant
Location: chr1:109630331 (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 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
AMPD2 c.353+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-pro694 (accessed [today's date]).

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