Is CIMIP6 p.Ile178Arg (c.533T>G) pathogenic?

CIMIP6 p.Ile178Arg (c.533T>G) is classified Uncertain significance in CIMIP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: ambiguous (0.3777); Very rare (popmax 0.0052%, amr).

How common is CIMIP6 p.Ile178Arg (c.533T>G) in the general population?

CIMIP6 p.Ile178Arg (c.533T>G) is very rare (popmax 0.0052%, amr) (gnomAD).

What do computational predictors say about CIMIP6 p.Ile178Arg (c.533T>G)?

AlphaMissense predicts ambiguous (score 0.3777) — an in-silico prediction, not a clinical call.

CIMIP6 p.Ile178Arg

c.533T>G · rs761545934 · VCV2206757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0052%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3777	ambiguous
REVEL	0.205	benign-leaning
SaProt	LLR -5.21	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 2.4	GERP 0.58, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 30 kb · p 0.0055 · regional, not allelic
Overall
CADD	23.8	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 0.0052% Admixed American · 3/57,724 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00181% 29/1,602,698 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0052%	19,241
African / African-American	0.0027%	37,105
East Asian	0.00223%	44,770
European (non-Finnish)	0.00196%	51,128

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: CIMIP6
Protein: p.Ile178Arg
Coding: c.533T>G
MANE Select: NM_001100396
dbSNP: rs761545934
Type: single nucleotide variant
Location: chr2:54360231 (GRCh38)
Structure: AlphaFold pLDDT 54.11

Full CIMIP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMIP6 p.Gly136Arg Uncertain significance ★ ⚠ same type
CIMIP6 p.Leu93Pro 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/cimip6-p-ile178arg (accessed [today's date]).

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