Is MAP1B p.Ile59Thr (c.176T>C) pathogenic?

MAP1B p.Ile59Thr (c.176T>C) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.7858); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Ile59Thr (c.176T>C)?

MAP1B p.Ile59Thr (c.176T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Ile59Thr (c.176T>C) in the general population?

MAP1B p.Ile59Thr (c.176T>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about MAP1B p.Ile59Thr (c.176T>C)?

AlphaMissense predicts likely pathogenic (score 0.7858) — an in-silico prediction, not a clinical call.

MAP1B p.Ile59Thr

c.176T>C · rs746137908 · VCV2542788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7858	likely pathogenic
REVEL	0.519	indeterminate
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 5.5, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 87 kb · p 3.4e-10 · regional, not allelic
Overall
CADD	27.7	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 0.0156% East Asian · 7/44,794 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.0005% 8/1,599,206 alleles · ultra-rare exomes 8/1,447,098 · genomes 0/152,108 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,399
Remaining individualsnot grpmax-eligible	0.0016%	62,352

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: MAP1B
Protein: p.Ile59Thr
Coding: c.176T>C
MANE Select: NM_005909
dbSNP: rs746137908
Type: single nucleotide variant
Location: chr5:72107707 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP1B p.Ile59Val Conflicting classifications of pathogenicity ★ ⚠ same residue
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1480Tyr Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1993Gly Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu2435Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly919Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly932Ser 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-ile59thr (accessed [today's date]).

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