Is ARAP3 p.Pro1209Ser (c.3625C>T) pathogenic?

ARAP3 p.Pro1209Ser (c.3625C>T) is classified Likely benign in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0548); Very rare (popmax 0.00446%, eas).

How common is ARAP3 p.Pro1209Ser (c.3625C>T) in the general population?

ARAP3 p.Pro1209Ser (c.3625C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ARAP3 p.Pro1209Ser (c.3625C>T)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

ARAP3 p.Pro1209Ser

c.3625C>T · VCV4130357

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -3.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.7	GERP -2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	12.73	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 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,611,734 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
African / African-American	0.00401%	24,966
Admixed American	0.00168%	59,494
Remaining individualsnot grpmax-eligible	0.0016%	62,422
European (non-Finnish)	8.48e-05%	1,178,992

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: ARAP3
Protein: p.Pro1209Ser
Coding: c.3625C>T
MANE Select: NM_022481
Type: single nucleotide variant
Location: chr5:141656748 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB
Residue 1209: the ras-associating domain

Full ARAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARAP3 p.Pro1209Thr Uncertain significance ★ ⚠ same residue
ARAP3 p.Ala1045Val Uncertain significance ★ ⚠ same type
ARAP3 p.Ala10Thr Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1159Val Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1276Ser Uncertain significance ★ ⚠ same type
ARAP3 p.Ala1342Thr Uncertain significance ★ ⚠ same type
ARAP3 p.Ala216Asp Uncertain significance ★ ⚠ same type
ARAP3 p.Ala22Val 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/arap3-p-pro1209ser (accessed [today's date]).

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