Is ARAP1 p.Arg148Trp (c.442C>T) pathogenic?

ARAP1 p.Arg148Trp (c.442C>T) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.2229); Rare (popmax 0.161%, afr).

How common is ARAP1 p.Arg148Trp (c.442C>T) in the general population?

ARAP1 p.Arg148Trp (c.442C>T) is rare (popmax 0.161%, afr) (gnomAD).

What do computational predictors say about ARAP1 p.Arg148Trp (c.442C>T)?

AlphaMissense predicts likely benign (score 0.2229) — an in-silico prediction, not a clinical call.

ARAP1 p.Arg148Trp

c.442C>T · VCV3309445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2229 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.161%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2229	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -11.59	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.75, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 477 bp · p 0.011 · regional, not allelic
Overall
CADD	21.3	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 0.161% African / African-American · 118/73,382 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.00846% 131/1,547,550 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.161%	622
Middle Eastern	0.0211%	4,750
Admixed American	0.00777%	12,866
East Asian	0.00482%	20,762
European (non-Finnish)	0.000524%	190,837

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.Arg148Trp
Coding: c.442C>T
MANE Select: NM_001040118
Type: single nucleotide variant
Location: chr11:72726687 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB

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

Similar variants

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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-arg148trp (accessed [today's date]).

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