Is ABLIM2 p.Arg595Leu (c.1784G>T) pathogenic?

ABLIM2 p.Arg595Leu (c.1784G>T) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely pathogenic (0.9194); Absent from gnomAD v4.1.

How common is ABLIM2 p.Arg595Leu (c.1784G>T) in the general population?

ABLIM2 p.Arg595Leu (c.1784G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABLIM2 p.Arg595Leu (c.1784G>T)?

AlphaMissense predicts likely pathogenic (score 0.9194) — an in-silico prediction, not a clinical call.

ABLIM2 p.Arg595Leu

c.1784G>T · VCV4636417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9194 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9194	likely pathogenic
REVEL	0.289	benign-leaning
SaProt	LLR -13.81	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R561L vs ClinVar R595L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABLIM2
Protein: p.Arg595Leu
Coding: c.1784G>T
MANE Select: NM_001130083
Type: single nucleotide variant
Location: chr4:7983304 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 595: the hp domain; an α-helix

Full ABLIM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABLIM2 p.Arg595Cys Uncertain significance ★ ⚠ same residue
ABLIM2 p.Arg595Gly Uncertain significance ★ ⚠ same residue
ABLIM2 p.Arg595His Uncertain significance ★ ⚠ same residue
ABLIM2 c.763+4C>T Benign ★★ same type
ABLIM2 c.763+5A>G Benign ★★ same type
ABLIM2 p.Ala144Thr Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala21Val Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala288Val 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/ablim2-p-arg595leu (accessed [today's date]).

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