Is ABLIM2 p.Arg375His (c.1124G>A) pathogenic?

ABLIM2 p.Arg375His (c.1124G>A) is classified Uncertain significance in ABLIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.0692); Ultra-rare (popmax 0.0202%, sas).

How common is ABLIM2 p.Arg375His (c.1124G>A) in the general population?

ABLIM2 p.Arg375His (c.1124G>A) is ultra-rare (popmax 0.0202%, sas) (gnomAD).

What do computational predictors say about ABLIM2 p.Arg375His (c.1124G>A)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

ABLIM2 p.Arg375His

c.1124G>A · rs547044955 · VCV2520481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -8.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 192 kb · p 0.27 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0202% South Asian · 17/84,060 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.00413% 64/1,550,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0202%	4,945
Middle Eastern	0.0167%	5,986
African / African-American	0.00958%	10,439
Admixed American	0.00392%	25,517
Remaining individualsnot grpmax-eligible	0.00333%	30,071
European (non-Finnish)	0.00296%	33,743
East Asian	0.00244%	40,920

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.Arg375His
Coding: c.1124G>A
MANE Select: NM_001130083
dbSNP: rs547044955
Type: single nucleotide variant
Location: chr4:8029700 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.21 · 3 PDB
Residue 375: the 'disordered' region

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-arg375his (accessed [today's date]).

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