Is ARK2C p.Arg236Gln (c.707G>A) pathogenic?

ARK2C p.Arg236Gln (c.707G>A) is classified Uncertain significance in ARK2C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.2174); Very rare (popmax 0.00533%, afr).

How common is ARK2C p.Arg236Gln (c.707G>A) in the general population?

ARK2C p.Arg236Gln (c.707G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about ARK2C p.Arg236Gln (c.707G>A)?

AlphaMissense predicts likely benign (score 0.2174) — an in-silico prediction, not a clinical call.

ARK2C p.Arg236Gln

c.707G>A · VCV3785085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2174	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -9.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 122 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	32.0	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 0.00533% African / African-American · 4/74,998 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00124% 20/1,611,234 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,749
South Asian	0.00439%	22,760
Remaining individualsnot grpmax-eligible	0.0032%	31,214
European (non-Finnish)	0.000849%	117,728

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: ARK2C
Protein: p.Arg236Gln
Coding: c.707G>A
MANE Select: NM_152470
Type: single nucleotide variant
Location: chr18:46450387 (GRCh38)
Structure: AlphaFold pLDDT 57.50 · 9 PDB

Full ARK2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARK2C p.Ala157Thr Uncertain significance ★ ⚠ same type
ARK2C p.Arg138Cys Uncertain significance ★ ⚠ same type
ARK2C p.Arg211Gln Uncertain significance ★ ⚠ same type
ARK2C p.Asn227Thr Uncertain significance ★ ⚠ same type
ARK2C p.Asp345Asn Uncertain significance ★ ⚠ same type
ARK2C p.Gln147His Uncertain significance ★ ⚠ same type
ARK2C p.Gln174Glu Uncertain significance ★ ⚠ same type
ARK2C p.Gln46Pro Uncertain significance ★ ⚠ same type

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/ark2c-p-arg236gln (accessed [today's date]).

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