Is ABI3BP p.Arg1663Ile (c.4988G>T) pathogenic?

ABI3BP p.Arg1663Ile (c.4988G>T) is classified Uncertain significance in ABI3BP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely benign (0.1091); Very rare (popmax 0.00102%, nfe).

How common is ABI3BP p.Arg1663Ile (c.4988G>T) in the general population?

ABI3BP p.Arg1663Ile (c.4988G>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about ABI3BP p.Arg1663Ile (c.4988G>T)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

ABI3BP p.Arg1663Ile

c.4988G>T · VCV3434611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.447	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 243 kb · p 0.048 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R952I vs ClinVar R1663I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,546 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000744% 12/1,613,014 alleles · very rare

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: ABI3BP
Protein: p.Arg1663Ile
Coding: c.4988G>T
MANE Select: NM_001375547
Type: single nucleotide variant
Location: chr3:100752921 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.33

Full ABI3BP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABI3BP p.Ala1237Thr Uncertain significance ★ ⚠ same type
ABI3BP p.Ala1342Val Uncertain significance ★ ⚠ same type
ABI3BP p.Ala1644Glu Uncertain significance ★ same type
ABI3BP p.Ala1644Val Uncertain significance ★ same type
ABI3BP p.Ala234Val Uncertain significance ★ ⚠ same type
ABI3BP p.Ala501Val Uncertain significance ★ same type
ABI3BP p.Arg113His Uncertain significance ★ ⚠ same type
ABI3BP p.Arg115Cys 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/abi3bp-p-arg1663ile (accessed [today's date]).

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