Is ABLIM2 p.Ile192Asn (c.575T>A) pathogenic?

ABLIM2 p.Ile192Asn (c.575T>A) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely pathogenic (0.9963); Ultra-rare (popmax 0.0147%, afr).

How common is ABLIM2 p.Ile192Asn (c.575T>A) in the general population?

ABLIM2 p.Ile192Asn (c.575T>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about ABLIM2 p.Ile192Asn (c.575T>A)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

ABLIM2 p.Ile192Asn

c.575T>A · VCV3793938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic · top 4% in ABLIM2
REVEL	0.861	moderately pathogenic-leaning
SaProt	LLR -14.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	28.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,796 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000748% 12/1,605,268 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,800
Admixed American	0.00168%	59,518

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.Ile192Asn
Coding: c.575T>A
MANE Select: NM_001130083
Type: single nucleotide variant
Location: chr4:8080682 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 192: the lim zinc-binding 3 domain

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

Similar variants

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
ABLIM2 p.Ala476Ser Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala565Asp Uncertain significance ★ ⚠ same type
ABLIM2 p.Ala97Val 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-ile192asn (accessed [today's date]).

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