Is ARAP1 p.Arg1434Trp (c.4300C>T) pathogenic?

ARAP1 p.Arg1434Trp (c.4300C>T) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). AlphaMissense: ambiguous (0.381); Ultra-rare (popmax 0.045%, sas).

How common is ARAP1 p.Arg1434Trp (c.4300C>T) in the general population?

ARAP1 p.Arg1434Trp (c.4300C>T) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about ARAP1 p.Arg1434Trp (c.4300C>T)?

AlphaMissense predicts ambiguous (score 0.381) — an in-silico prediction, not a clinical call.

ARAP1 p.Arg1434Trp

c.4300C>T · VCV3419333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.381 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.381	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -9.24	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 4.7	GERP 0.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	28.6	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 0.045% South Asian · 41/91,088 alleles

Filtering AF 0.034% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00366% 59/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,222
Admixed American	0.00999%	10,006
African / African-American	0.008%	12,506
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.000424%	236,007

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.Arg1434Trp
Coding: c.4300C>T
MANE Select: NM_001040118
Type: single nucleotide variant
Location: chr11:72686077 (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
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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-arg1434trp (accessed [today's date]).

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