Is ARAP2 p.Asp10Asn (c.28G>A) pathogenic?

ARAP2 p.Asp10Asn (c.28G>A) is classified Likely benign in ARAP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-01). AlphaMissense: likely benign (0.0859); Low-frequency (popmax 1.54%, mid).

How common is ARAP2 p.Asp10Asn (c.28G>A) in the general population?

ARAP2 p.Asp10Asn (c.28G>A) is low-frequency (popmax 1.54%, mid) (gnomAD).

What do computational predictors say about ARAP2 p.Asp10Asn (c.28G>A)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

ARAP2 p.Asp10Asn

c.28G>A · rs147255071 · VCV2654709

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -7.36	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 6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 162 kb · p 0.0019 · regional, not allelic
Overall
CADD	22.4	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 1.54% Middle Eastern · 93/6,052 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.162% 2,614/1,611,504 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.54%	65
South Asian	0.527%	190
Remaining individualsnot grpmax-eligible	0.256%	390
Ashkenazi Jewishnot grpmax-eligible	0.197%	508
European (non-Finnish)	0.147%	679
Admixed American	0.107%	935
African / African-American	0.0227%	4,409
Finnishnot grpmax-eligible	0.00782%	12,780
East Asian	0.00446%	22,408

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.Asp10Asn
Coding: c.28G>A
MANE Select: NM_015230
dbSNP: rs147255071
Type: single nucleotide variant
Location: chr4:36229459 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.42 · 2 PDB
Residue 10: the sam domain

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

Similar variants

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
ARAP2 p.Ala1508Thr 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-asp10asn (accessed [today's date]).

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