Is ADK p.Asp235= (c.705T>C) pathogenic?

ADK p.Asp235= (c.705T>C) is classified Benign in ADK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Common (popmax 9.29%, afr) — too common for a highly-penetrant pathogenic allele; Associated with adenosine kinase deficiency.

What condition is associated with ADK p.Asp235= (c.705T>C)?

ADK p.Asp235= (c.705T>C) is associated with adenosine kinase deficiency (ClinVar).

ADK p.Asp235=

Q: How common is ADK p.Asp235= (c.705T>C) in the general population?

ADK p.Asp235= (c.705T>C) is common (popmax 9.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.705T>C · rs16931480 · VCV300839

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 9.29%, afr) — too common for a highly-penetrant pathogenic allele

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 1.8	GERP 0.32, phastCons 1
Overall
CADD	10.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.29% African / African-American · 6,970/74,992 alleles

Filtering AF 9.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.04%

Overall 0.848% 13,685/1,613,050 alleles · common exomes 9,170/1,460,764 · genomes 4,515/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.29%	11
Middle Eastern	2.11%	47
Ashkenazi Jewishnot grpmax-eligible	1.97%	51
South Asian	1.94%	52
Finnishnot grpmax-eligible	1.61%	62
Remaining individualsnot grpmax-eligible	1.24%	81
Admixed American	0.751%	133
European (non-Finnish)	0.169%	593
East Asian	0.00447%	22,385

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.Asp235=
Coding: c.705T>C
MANE Select: NM_006721
dbSNP: rs16931480
Type: single nucleotide variant
Location: chr10:74525405 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB
Residue 235: a UniProt-annotated variant site (in hmakd); a UniProt-annotated variant site (in hmakd; abolished ability to mediate phosphorylation of unmodified and modified adenosines); a β-strand

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.Asp235Ala Pathogenic same residue
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

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-asp235 (accessed [today's date]).

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