Is AMPD2 p.Val567Ala (c.1700T>C) pathogenic?

AMPD2 p.Val567Ala (c.1700T>C) is classified Uncertain significance in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely pathogenic (0.7108); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMPD2 p.Val567Ala (c.1700T>C)?

AMPD2 p.Val567Ala (c.1700T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AMPD2 p.Val567Ala (c.1700T>C) in the general population?

AMPD2 p.Val567Ala (c.1700T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AMPD2 p.Val567Ala (c.1700T>C)?

AlphaMissense predicts likely pathogenic (score 0.7108) — an in-silico prediction, not a clinical call.

AMPD2 p.Val567Ala

c.1700T>C · rs754636327 · VCV2284739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7108 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7108	likely pathogenic
REVEL	0.835	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 0.72, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,009 bp · p 8.7e-13 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 V621A vs ClinVar V567A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 0.000248% 4/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868
European (non-Finnish)grpmax	8.47e-05%	1,180,011

Ashkenazi Jewish 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.Val567Ala
Coding: c.1700T>C
MANE Select: NM_001368809
dbSNP: rs754636327
Type: single nucleotide variant
Location: chr1:109629328 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 567: a β-strand

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-val567ala (accessed [today's date]).

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