Is ABLIM2 p.Arg595Cys (c.1783C>T) pathogenic?

ABLIM2 p.Arg595Cys (c.1783C>T) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely pathogenic (0.8499); Very rare (popmax 0.00774%, sas).

How common is ABLIM2 p.Arg595Cys (c.1783C>T) in the general population?

ABLIM2 p.Arg595Cys (c.1783C>T) is very rare (popmax 0.00774%, sas) (gnomAD).

What do computational predictors say about ABLIM2 p.Arg595Cys (c.1783C>T)?

AlphaMissense predicts likely pathogenic (score 0.8499) — an in-silico prediction, not a clinical call.

ABLIM2 p.Arg595Cys

c.1783C>T · VCV3438410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8499 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00774%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8499	likely pathogenic
REVEL	0.246	benign-leaning
SaProt	LLR -13.70	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	29.8	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 R561C vs ClinVar R595C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00774% South Asian · 7/90,424 alleles

Filtering AF 0.00361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.00353% 57/1,612,474 alleles · very rare exomes 54/1,460,334 · genomes 3/152,140 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00801%	12,488
South Asiangrpmax	0.00774%	12,918
African / African-American	0.00534%	18,724
European (non-Finnish)	0.00331%	30,245
East Asian	0.00223%	44,852
Finnishnot grpmax-eligible	0.00156%	63,942

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg595Cys
Coding: c.1783C>T
MANE Select: NM_001130083
Type: single nucleotide variant
Location: chr4:7983305 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 561 UniProt numbering: the hp domain; a turn

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

Similar variants

ABLIM2 p.Arg595Gly Uncertain significance ★ ⚠ same residue
ABLIM2 p.Arg595His 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-arg595cys (accessed [today's date]).

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