Is ARAP1 p.Ile1191Phe (c.3571A>T) pathogenic?

ARAP1 p.Ile1191Phe (c.3571A>T) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). AlphaMissense: ambiguous (0.3898); Ultra-rare (popmax 0.0132%, nfe).

How common is ARAP1 p.Ile1191Phe (c.3571A>T) in the general population?

ARAP1 p.Ile1191Phe (c.3571A>T) is ultra-rare (popmax 0.0132%, nfe) (gnomAD).

What do computational predictors say about ARAP1 p.Ile1191Phe (c.3571A>T)?

AlphaMissense predicts ambiguous (score 0.3898) — an in-silico prediction, not a clinical call.

ARAP1 p.Ile1191Phe

c.3571A>T · rs149283425 · VCV2352523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3898 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3898	ambiguous
REVEL	0.094	moderately benign-leaning
SaProt	LLR -8.40	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.021	GERP -4.3, phastCons 0.002
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	15.08	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 0.0132% European (non-Finnish) · 156/1,180,038 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.0103% 167/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0132%	7,564
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.00534%	18,734

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.Ile1191Phe
Coding: c.3571A>T
MANE Select: NM_001040118
dbSNP: rs149283425
Type: single nucleotide variant
Location: chr11:72695392 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB
Residue 1191: the ras-associating 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-ile1191phe (accessed [today's date]).

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