Is ARAP3 p.Arg706Cys (c.2116C>T) pathogenic?

ARAP3 p.Arg706Cys (c.2116C>T) is classified Uncertain significance in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely benign (0.2167); Very rare (popmax 0.0041%, afr).

How common is ARAP3 p.Arg706Cys (c.2116C>T) in the general population?

ARAP3 p.Arg706Cys (c.2116C>T) is very rare (popmax 0.0041%, afr) (gnomAD).

What do computational predictors say about ARAP3 p.Arg706Cys (c.2116C>T)?

AlphaMissense predicts likely benign (score 0.2167) — an in-silico prediction, not a clinical call.

ARAP3 p.Arg706Cys

c.2116C>T · rs1264379093 · VCV2552073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2167	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -9.88	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 3.6	GERP 0.16, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	27.0	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 0.0041% African / African-American · 3/73,208 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.000691% 11/1,591,792 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0041%	24,403
East Asian	0.00223%	44,838
European (non-Finnish)	0.000596%	167,796

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: ARAP3
Protein: p.Arg706Cys
Coding: c.2116C>T
MANE Select: NM_022481
dbSNP: rs1264379093
Type: single nucleotide variant
Location: chr5:141670055 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB

Full ARAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ARAP3 p.Ala1276Ser Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1342Thr Uncertain significance ★ ⚠ same type
ARAP3 p.Ala216Asp Uncertain significance ★ ⚠ same type
ARAP3 p.Ala22Val Uncertain significance ★ ⚠ same type
ARAP3 p.Ala36Thr 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/arap3-p-arg706cys (accessed [today's date]).

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