Is ARAP2 p.Arg271Cys (c.811C>T) pathogenic?

ARAP2 p.Arg271Cys (c.811C>T) is classified Uncertain significance in ARAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1113); Ultra-rare (popmax 0.02%, amr).

How common is ARAP2 p.Arg271Cys (c.811C>T) in the general population?

ARAP2 p.Arg271Cys (c.811C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about ARAP2 p.Arg271Cys (c.811C>T)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

ARAP2 p.Arg271Cys

c.811C>T · rs754428866 · VCV2360920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -8.56	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 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 162 kb · p 0.0019 · regional, not allelic
Overall
CADD	18.7	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 0.02% Admixed American · 12/59,974 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00235% 38/1,613,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,998
African / African-American	0.00801%	12,482
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00136%	73,747

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: ARAP2
Protein: p.Arg271Cys
Coding: c.811C>T
MANE Select: NM_015230
dbSNP: rs754428866
Type: single nucleotide variant
Location: chr4:36228676 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.42 · 2 PDB

Full ARAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARAP2 p.Arg271His Uncertain significance ★ ⚠ same residue
ARAP2 p.Ala1241Thr Uncertain significance ★ ⚠ same type
ARAP2 p.Ala1261Thr Uncertain significance ★ ⚠ same type
ARAP2 p.Ala1261Val Uncertain significance ★ ⚠ same type
ARAP2 p.Ala1353Glu Uncertain significance ★ ⚠ same type
ARAP2 p.Ala1375Pro Uncertain significance ★ ⚠ same type
ARAP2 p.Ala1421Ser Uncertain significance ★ ⚠ same type
ARAP2 p.Ala1421Thr 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/arap2-p-arg271cys (accessed [today's date]).

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