Is IMMT p.Arg366Trp (c.1096C>T) pathogenic?

IMMT p.Arg366Trp (c.1096C>T) is classified Uncertain significance in IMMT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: ambiguous (0.4804); Very rare (popmax 0.0034%, amr).

How common is IMMT p.Arg366Trp (c.1096C>T) in the general population?

IMMT p.Arg366Trp (c.1096C>T) is very rare (popmax 0.0034%, amr) (gnomAD).

What do computational predictors say about IMMT p.Arg366Trp (c.1096C>T)?

AlphaMissense predicts ambiguous (score 0.4804) — an in-silico prediction, not a clinical call.

IMMT p.Arg366Trp

c.1096C>T · rs373860527 · VCV2335858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0034%, amr)

Computational evidence

Protein change
AlphaMissense	0.4804	ambiguous
REVEL	0.38	indeterminate
SaProt	LLR -8.73	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 51 kb · p 0.0073 · regional, not allelic
Overall
CADD	28.4	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 0.0034% Admixed American · 2/58,758 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000436% 7/1,604,206 alleles · very rare exomes 5/1,452,112 · genomes 2/152,094 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0034%	29,379
European (non-Finnish)	0.000426%	235,002

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: IMMT
Protein: p.Arg366Trp
Coding: c.1096C>T
MANE Select: NM_006839
dbSNP: rs373860527
Type: single nucleotide variant
Location: chr2:86158658 (GRCh38)
Gene constraint: LOEUF 0.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81 · 1 PDB

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

Similar variants

IMMT c.119+4T>C Benign ★★ same type
IMMT p.Glu435Lys Likely benign ★★ same type
IMMT p.Thr171= Benign ★★ same type
IMMT p.Ala227Gly Uncertain significance ★ ⚠ same type
IMMT p.Ala259Thr Uncertain significance ★ same type
IMMT p.Ala347Thr Uncertain significance ★ ⚠ same type
IMMT p.Ala444Val Uncertain significance ★ ⚠ same type
IMMT p.Ala462Val 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/immt-p-arg366trp (accessed [today's date]).

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