Is MAP1B p.Thr596Ile (c.1787C>T) pathogenic?

MAP1B p.Thr596Ile (c.1787C>T) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely benign (0.1406); Absent from gnomAD v4.1; Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Thr596Ile (c.1787C>T)?

MAP1B p.Thr596Ile (c.1787C>T) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Thr596Ile (c.1787C>T) in the general population?

MAP1B p.Thr596Ile (c.1787C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP1B p.Thr596Ile (c.1787C>T)?

AlphaMissense predicts likely benign (score 0.1406) — an in-silico prediction, not a clinical call.

MAP1B p.Thr596Ile

c.1787C>T · rs1580020679 · VCV2635150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1406 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAP1B-related disorder

Computational evidence

Protein change
AlphaMissense	0.1406	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -0.63, phastCons 0.005
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	18.43	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP1B
Protein: p.Thr596Ile
Coding: c.1787C>T
MANE Select: NM_005909
dbSNP: rs1580020679
Type: single nucleotide variant
Location: chr5:72195142 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 596: the 'disordered' region; a UniProt-annotated variant site (in pvnh9)

Full MAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAP1B-related disorder

Similar variants

MAP1B p.Pro1182Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Thr2194Met Uncertain significance ★★ ⚠ same condition
MAP1B p.Gln325Ter Likely pathogenic ★ same condition
MAP1B p.Lys751Ter Likely pathogenic ★ same condition
MAP1B p.Arg64Gln Uncertain significance ★ same condition
MAP1B p.Asp1637Asn Uncertain significance ★ ⚠ same condition
MAP1B p.Glu678Gly Uncertain significance ★ ⚠ same condition
MAP1B p.Glu927Asp Uncertain significance ★ ⚠ same condition

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/map1b-p-thr596ile (accessed [today's date]).

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