Is ARAP1 p.His1278Arg (c.3833A>G) pathogenic?

ARAP1 p.His1278Arg (c.3833A>G) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: likely pathogenic (0.7431); Very rare (popmax 0.00668%, afr).

How common is ARAP1 p.His1278Arg (c.3833A>G) in the general population?

ARAP1 p.His1278Arg (c.3833A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about ARAP1 p.His1278Arg (c.3833A>G)?

AlphaMissense predicts likely pathogenic (score 0.7431) — an in-silico prediction, not a clinical call.

ARAP1 p.His1278Arg

c.3833A>G · rs1687046024 · VCV2350182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7431 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7431	likely pathogenic
REVEL	0.18	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	26.0	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 0.00668% African / African-American · 5/74,890 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00031% 5/1,613,510 alleles · very rare

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: ARAP1
Protein: p.His1278Arg
Coding: c.3833A>G
MANE Select: NM_001040118
dbSNP: rs1687046024
Type: single nucleotide variant
Location: chr11:72693446 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB
Residue 1278: the ph 4 domain

Full ARAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARAP1 p.Gln1047Glu Benign ★★ same type
ARAP1 p.Pro1039= Benign ★★ same type
ARAP1 p.Pro254Leu Benign ★★ same type
ARAP1 p.Val1408Met Benign ★★ ⚠ same type
ARAP1 p.Ala1046Ser Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1124Thr Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1199Thr Uncertain significance ★ ⚠ same type
ARAP1 p.Ala1389Thr 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/arap1-p-his1278arg (accessed [today's date]).

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