Is ABLIM2 p.Arg595His (c.1784G>A) pathogenic?

ABLIM2 p.Arg595His (c.1784G>A) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.6153); Very rare (popmax 0.00892%, eas).

How common is ABLIM2 p.Arg595His (c.1784G>A) in the general population?

ABLIM2 p.Arg595His (c.1784G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about ABLIM2 p.Arg595His (c.1784G>A)?

AlphaMissense predicts likely pathogenic (score 0.6153) — an in-silico prediction, not a clinical call.

ABLIM2 p.Arg595His

c.1784G>A · rs750016618 · VCV623406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6153	likely pathogenic
REVEL	0.316	indeterminate
SaProt	LLR -12.86	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R561H vs ClinVar R595H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,848 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00377% 55/1,460,322 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,212
South Asian	0.00442%	22,599
European (non-Finnish)	0.00356%	28,084
Remaining individualsnot grpmax-eligible	0.0032%	31,225
Finnishnot grpmax-eligible	0.00313%	31,972
African / African-American	0.00133%	74,976

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: ABLIM2
Protein: p.Arg595His
Coding: c.1784G>A
MANE Select: NM_001130083
dbSNP: rs750016618
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.Arg595Leu 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-arg595his (accessed [today's date]).

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