Is ABLIM3 p.Arg323His (c.968G>A) pathogenic?

ABLIM3 p.Arg323His (c.968G>A) is classified Uncertain significance in ABLIM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.1333); Ultra-rare (popmax 0.012%, afr).

How common is ABLIM3 p.Arg323His (c.968G>A) in the general population?

ABLIM3 p.Arg323His (c.968G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about ABLIM3 p.Arg323His (c.968G>A)?

AlphaMissense predicts likely benign (score 0.1333) — an in-silico prediction, not a clinical call.

ABLIM3 p.Arg323His

c.968G>A · rs149749871 · VCV3132357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1333 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1333	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -8.96	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 6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 116 kb · p 0.0017 · regional, not allelic
Overall
CADD	25.9	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 0.012% African / African-American · 9/74,866 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00155% 25/1,613,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,318
Admixed American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0064%	15,620
East Asian	0.00223%	44,892
South Asian	0.0011%	91,088
European (non-Finnish)	0.000508%	196,672

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: ABLIM3
Protein: p.Arg323His
Coding: c.968G>A
MANE Select: NM_014945
dbSNP: rs149749871
Type: single nucleotide variant
Location: chr5:149237527 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.31 · 2 PDB

Full ABLIM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABLIM3 p.Arg323Cys Uncertain significance ★ ⚠ same residue
ABLIM3 p.Arg513Cys Uncertain significance ★★ ⚠ same type
ABLIM3 p.Ala166Gly Uncertain significance ★ ⚠ same type
ABLIM3 p.Ala297Val Uncertain significance ★ ⚠ same type
ABLIM3 p.Ala371Asp Uncertain significance ★ ⚠ same type
ABLIM3 p.Ala600Pro Uncertain significance ★ ⚠ same type
ABLIM3 p.Arg15Trp Uncertain significance ★ ⚠ same type
ABLIM3 p.Arg215Gln 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/ablim3-p-arg323his (accessed [today's date]).

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