Is IMMT p.Cys603Phe (c.1808G>T) pathogenic?

IMMT p.Cys603Phe (c.1808G>T) is classified Uncertain significance in IMMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.2553); Ultra-rare (popmax 0.01%, amr).

How common is IMMT p.Cys603Phe (c.1808G>T) in the general population?

IMMT p.Cys603Phe (c.1808G>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about IMMT p.Cys603Phe (c.1808G>T)?

AlphaMissense predicts likely benign (score 0.2553) — an in-silico prediction, not a clinical call.

IMMT p.Cys603Phe

c.1808G>T · rs771180473 · VCV3109534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2553 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2553	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -3.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 51 kb · p 0.0073 · regional, not allelic
Overall
CADD	26.4	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 0.01% Admixed American · 6/59,998 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,800 alleles · ultra-rare exomes 5/1,461,638 · genomes 1/152,162 · joint denominator

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.Cys603Phe
Coding: c.1808G>T
MANE Select: NM_006839
dbSNP: rs771180473
Type: single nucleotide variant
Location: chr2:86144737 (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-cys603phe (accessed [today's date]).

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