Is CIMIP2B p.Arg58His (c.173G>A) pathogenic?

CIMIP2B p.Arg58His (c.173G>A) is classified Uncertain significance in CIMIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0826); Ultra-rare (popmax 0.0111%, eas).

How common is CIMIP2B p.Arg58His (c.173G>A) in the general population?

CIMIP2B p.Arg58His (c.173G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CIMIP2B p.Arg58His (c.173G>A)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

CIMIP2B p.Arg58His

c.173G>A · rs780659260 · VCV2212830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.62	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 2.2	GERP -0.3, phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 1,818 bp · p 0.2 · regional, not allelic
Overall
CADD	19.63	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 0.0111% East Asian · 5/44,902 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00446% 72/1,613,760 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,980
African / African-American	0.00935%	10,700
Remaining individualsnot grpmax-eligible	0.0048%	20,820
European (non-Finnish)	0.00466%	21,452
Admixed American	0.00167%	59,978
Finnishnot grpmax-eligible	0.00156%	64,006

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: CIMIP2B
Protein: p.Arg58His
Coding: c.173G>A
MANE Select: NM_001164310
dbSNP: rs780659260
Type: single nucleotide variant
Location: chr9:35563279 (GRCh38)
Structure: AlphaFold pLDDT 68.93 · 2 PDB

Full CIMIP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMIP2B p.Arg58Cys Uncertain significance ★ ⚠ same residue
RUSC2 p.Cys1328Tyr Uncertain significance ★★ ⚠ same type
CIMIP2B p.Ala114Val Uncertain significance ★ ⚠ same type
CIMIP2B p.Ala165Thr Uncertain significance ★ ⚠ same type
CIMIP2B p.Ala190Thr Uncertain significance ★ ⚠ same type
CIMIP2B p.Ala2Val Uncertain significance ★ ⚠ same type
CIMIP2B p.Arg100Trp Uncertain significance ★ ⚠ same type
CIMIP2B p.Arg176Trp 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/cimip2b-p-arg58his (accessed [today's date]).

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