Is AMPD2 p.Met201Val (c.601A>G) pathogenic?

AMPD2 p.Met201Val (c.601A>G) is classified Uncertain significance in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: likely benign (0.1791); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with AMPD2 p.Met201Val (c.601A>G)?

AMPD2 p.Met201Val (c.601A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AMPD2 p.Met201Val (c.601A>G) in the general population?

AMPD2 p.Met201Val (c.601A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AMPD2 p.Met201Val (c.601A>G)?

AlphaMissense predicts likely benign (score 0.1791) — an in-silico prediction, not a clinical call.

AMPD2 p.Met201Val

c.601A>G · rs1466494219 · VCV2611812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1791 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1791	likely benign
REVEL	0.451	indeterminate
Splicing
SpliceAI	Δ0.28	donor gain, 5 bp away · raw score · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,721 bp · p 0.065 · regional, not allelic
Overall
CADD	25.3	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 M255V vs ClinVar M201V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,686 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
European (non-Finnish)	0.00017%	589,957

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.Met201Val
Coding: c.601A>G
MANE Select: NM_001368809
dbSNP: rs1466494219
Type: single nucleotide variant
Location: chr1:109626795 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 201: 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 p.Met201Thr Uncertain significance ★ 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-met201val (accessed [today's date]).

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