Is CIMIP2B p.Val245Met (c.733G>A) pathogenic?

CIMIP2B p.Val245Met (c.733G>A) is classified Uncertain significance in CIMIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: ambiguous (0.3993); Very rare (popmax 0.00241%, eas).

How common is CIMIP2B p.Val245Met (c.733G>A) in the general population?

CIMIP2B p.Val245Met (c.733G>A) is very rare (popmax 0.00241%, eas) (gnomAD).

What do computational predictors say about CIMIP2B p.Val245Met (c.733G>A)?

AlphaMissense predicts ambiguous (score 0.3993) — an in-silico prediction, not a clinical call.

CIMIP2B p.Val245Met

c.733G>A · rs763217295 · VCV3235599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00241%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3993	ambiguous
REVEL	0.29	benign-leaning
SaProt	LLR -9.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.75, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,818 bp · p 0.2 · regional, not allelic
Overall
CADD	24.8	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 0.00241% East Asian · 1/41,422 alleles

Filtering AF 0.00162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00218% 29/1,327,792 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00241%	41,422
European (non-Finnish)	0.00233%	42,877
Remaining individualsnot grpmax-eligible	0.00176%	56,976
South Asian	0.00144%	69,576

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.Val245Met
Coding: c.733G>A
MANE Select: NM_001164310
dbSNP: rs763217295
Type: single nucleotide variant
Location: chr9:35562386 (GRCh38)
Structure: AlphaFold pLDDT 68.93 · 2 PDB

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

Similar variants

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
CIMIP2B p.Arg46Gln 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-val245met (accessed [today's date]).

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