Is ARAP1 p.Arg370Cys (c.1108C>T) pathogenic?

ARAP1 p.Arg370Cys (c.1108C>T) is classified Uncertain significance in ARAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.5544); Ultra-rare (popmax 0.025%, amr).

How common is ARAP1 p.Arg370Cys (c.1108C>T) in the general population?

ARAP1 p.Arg370Cys (c.1108C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about ARAP1 p.Arg370Cys (c.1108C>T)?

AlphaMissense predicts ambiguous (score 0.5544) — an in-silico prediction, not a clinical call.

ARAP1 p.Arg370Cys

c.1108C>T · rs200779197 · VCV2350845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5544 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5544	ambiguous
REVEL	0.286	benign-leaning
SaProt	LLR -9.19	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 15 kb · p 7.9e-09 · regional, not allelic
Overall
CADD	32.0	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 0.025% Admixed American · 15/60,008 alleles

Filtering AF 0.0197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.0177% 285/1,614,056 alleles · ultra-rare exomes 260/1,461,882 · genomes 25/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,001
European (non-Finnish)	0.0219%	4,556
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00667%	14,983

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.Arg370Cys
Coding: c.1108C>T
MANE Select: NM_001040118
dbSNP: rs200779197
Type: single nucleotide variant
Location: chr11:72711126 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 1 PDB
Residue 370: the ph 1 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-arg370cys (accessed [today's date]).

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