Is ADK p.Ala344Val (c.1031C>T) pathogenic?

ADK p.Ala344Val (c.1031C>T) is classified Pathogenic/Likely pathogenic in ADK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-18). AlphaMissense: likely pathogenic (0.9604); Absent from gnomAD v4.1; Associated with adenosine kinase deficiency.

What condition is associated with ADK p.Ala344Val (c.1031C>T)?

ADK p.Ala344Val (c.1031C>T) is associated with adenosine kinase deficiency (ClinVar).

How common is ADK p.Ala344Val (c.1031C>T) in the general population?

ADK p.Ala344Val (c.1031C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADK p.Ala344Val (c.1031C>T)?

AlphaMissense predicts likely pathogenic (score 0.9604) — an in-silico prediction, not a clinical call.

ADK p.Ala344Val

Q: How is Hypermethioninemia encephalopathy due to adenosine kinase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1031C>T · rs1589387419 · VCV802589

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9604 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,928)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adenosine kinase deficiency

Computational evidence

Protein change
AlphaMissense	0.9604	likely pathogenic ✓ concordant with ClinVar
REVEL	0.904	moderately pathogenic-leaning
SaProt	LLR -12.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 557 kb · p 4.5e-07 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,928). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADK
Protein: p.Ala344Val
Coding: c.1031C>T
MANE Select: NM_006721
dbSNP: rs1589387419
Type: single nucleotide variant
Location: chr10:74708387 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB
Residue 344: a UniProt-annotated variant site (in hmakd); an α-helix

Full ADK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

adenosine kinase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypermethioninemia encephalopathy due to adenosine kinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

ADK p.Ile87Val Uncertain significance ★★ ⚠ same condition
ADK p.Lys74Glu Uncertain significance ★★ ⚠ same condition
ADK c.195-18A>G Benign/Likely benign ★★ same condition
ADK c.274-9G>T Likely benign ★★ same condition
ADK c.66-23911C>T Benign ★★ same condition
ADK c.726+11T>G Benign/Likely benign ★★ same condition
ADK c.727-11T>C Benign ★★ same condition
ADK c.878-71T>C Benign ★★ 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/adk-p-ala344val (accessed [today's date]).

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