Is ADK p.Ser329= (c.987T>C) pathogenic?

ADK p.Ser329= (c.987T>C) is classified Benign/Likely benign in ADK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Low-frequency (popmax 1.57%, afr); Associated with adenosine kinase deficiency.

What condition is associated with ADK p.Ser329= (c.987T>C)?

ADK p.Ser329= (c.987T>C) is associated with adenosine kinase deficiency (ClinVar).

How common is ADK p.Ser329= (c.987T>C) in the general population?

ADK p.Ser329= (c.987T>C) is low-frequency (popmax 1.57%, afr) (gnomAD).

ADK p.Ser329=

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.987T>C · rs116653664 · VCV716932

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, afr)

Conditions

adenosine kinase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -4.8
Overall
CADD	5.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.57% African / African-American · 1,176/74,916 alleles

Filtering AF 1.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.47%

Overall 0.084% 1,354/1,611,802 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.57%	64
Admixed American	0.127%	789
Remaining individualsnot grpmax-eligible	0.107%	932
Middle Eastern	0.0825%	1,212
South Asian	0.0132%	7,588
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,558
European (non-Finnish)	0.00144%	69,369

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: ADK
Protein: p.Ser329=
Coding: c.987T>C
MANE Select: NM_006721
dbSNP: rs116653664
Type: single nucleotide variant
Location: chr10:74708343 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB
Residue 329: a UniProt-annotated variant site (in hmakd); a turn

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.Ala344Val Pathogenic/Likely pathogenic ★★ same condition
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

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-ser329 (accessed [today's date]).

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