Is ABLIM2 p.Ile258Met (c.774C>G) pathogenic?

ABLIM2 p.Ile258Met (c.774C>G) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: ambiguous (0.3608); Rare (popmax 0.139%, nfe).

How common is ABLIM2 p.Ile258Met (c.774C>G) in the general population?

ABLIM2 p.Ile258Met (c.774C>G) is rare (popmax 0.139%, nfe) (gnomAD).

What do computational predictors say about ABLIM2 p.Ile258Met (c.774C>G)?

AlphaMissense predicts ambiguous (score 0.3608) — an in-silico prediction, not a clinical call.

ABLIM2 p.Ile258Met

c.774C>G · rs185934307 · VCV3132187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3608 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.139%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3608	ambiguous
REVEL	0.377	indeterminate
SaProt	LLR -12.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -0.98, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.139% European (non-Finnish) · 1,643/1,179,892 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.108% 1,741/1,614,066 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.139%	718
Admixed American	0.0716%	1,396
Remaining individualsnot grpmax-eligible	0.0688%	1,453
African / African-American	0.0133%	7,508
Finnishnot grpmax-eligible	0.00312%	32,009

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.Ile258Met
Coding: c.774C>G
MANE Select: NM_001130083
dbSNP: rs185934307
Type: single nucleotide variant
Location: chr4:8054236 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 258: the lim zinc-binding 4 domain; a β-strand

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-ile258met (accessed [today's date]).

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