Is ARAP3 p.Pro83Ser (c.247C>T) pathogenic?

ARAP3 p.Pro83Ser (c.247C>T) is classified Likely benign in ARAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: likely benign (0.064); Very rare (popmax 0.00133%, afr).

How common is ARAP3 p.Pro83Ser (c.247C>T) in the general population?

ARAP3 p.Pro83Ser (c.247C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ARAP3 p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely benign (score 0.064) — an in-silico prediction, not a clinical call.

ARAP3 p.Pro83Ser

c.247C>T · rs1167991796 · VCV3128269

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.064	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.1, phastCons 0.72
Regional constraint	o/e 0.93	unconstrained · MANE · 8,347 bp · p 0.061 · regional, not allelic
Overall
CADD	4.748	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 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,942 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.000169%	589,981

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.Pro83Ser
Coding: c.247C>T
MANE Select: NM_022481
dbSNP: rs1167991796
Type: single nucleotide variant
Location: chr5:141680240 (GRCh38)
Gene constraint: LOEUF 0.598 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 7 PDB
Residue 83: the 'disordered' region

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

Similar variants

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
ARAP3 p.Ala36Thr 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-pro83ser (accessed [today's date]).

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