Is ADK p.Glu7Asp (c.21G>C) pathogenic?

ADK p.Glu7Asp (c.21G>C) is classified Uncertain significance in ADK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1079); Very rare (popmax 0.00588%, amr); Associated with Inborn genetic diseases.

What condition is associated with ADK p.Glu7Asp (c.21G>C)?

ADK p.Glu7Asp (c.21G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ADK p.Glu7Asp (c.21G>C) in the general population?

ADK p.Glu7Asp (c.21G>C) is very rare (popmax 0.00588%, amr) (gnomAD).

What do computational predictors say about ADK p.Glu7Asp (c.21G>C)?

AlphaMissense predicts likely benign (score 0.1079) — an in-silico prediction, not a clinical call.

ADK p.Glu7Asp

c.21G>C · rs971684446 · VCV2218047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1079 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1079	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.6, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 557 kb · p 4.5e-07 · regional, not allelic
Overall
CADD	19.73	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00588% Admixed American · 3/50,994 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000833%

Overall 0.000215% 3/1,397,336 alleles · very rare

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.Glu7Asp
Coding: c.21G>C
MANE Select: NM_006721
dbSNP: rs971684446
Type: single nucleotide variant
Location: chr10:74151299 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB

Full ADK 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

ADK p.Arg338Cys Uncertain significance ★★ ⚠ same condition
ADK p.Arg338His Uncertain significance ★★ ⚠ same condition
ADK p.Asn53Asp Uncertain significance ★★ ⚠ same condition
ADK p.Asp305Glu Uncertain significance ★★ ⚠ same condition
ADK p.Gln306Leu Uncertain significance ★★ ⚠ same condition
ADK p.Lys264Asn Uncertain significance ★★ same condition
ADK p.Lys307Glu Uncertain significance ★★ ⚠ same condition
ADK p.Pro332Ser 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/adk-p-glu7asp (accessed [today's date]).

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