Is ADK p.Arg338His (c.1013G>A) pathogenic?

ADK p.Arg338His (c.1013G>A) is classified Uncertain significance in ADK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). AlphaMissense: likely benign (0.1125); Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with ADK p.Arg338His (c.1013G>A)?

ADK p.Arg338His (c.1013G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADK p.Arg338His (c.1013G>A) in the general population?

ADK p.Arg338His (c.1013G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about ADK p.Arg338His (c.1013G>A)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

ADK p.Arg338His

c.1013G>A · rs751608368 · VCV2160634

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.473	indeterminate
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 557 kb · p 4.5e-07 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.00935% African / African-American · 7/74,884 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00478% 77/1,612,300 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,698
East Asian	0.00669%	14,943
Admixed American	0.00668%	14,981
South Asian	0.00659%	15,175
Remaining individualsnot grpmax-eligible	0.0048%	20,813
European (non-Finnish)	0.00458%	21,842

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.Arg338His
Coding: c.1013G>A
MANE Select: NM_006721
dbSNP: rs751608368
Type: single nucleotide variant
Location: chr10:74708369 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.40 · 7 PDB
Residue 338: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADK p.Arg338Cys Uncertain significance ★★ ⚠ same residue
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
ADK p.Asn240Ser 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-arg338his (accessed [today's date]).

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