Is MAP1B p.Ile378Thr (c.1133T>C) pathogenic?

MAP1B p.Ile378Thr (c.1133T>C) is classified Likely benign in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0861); Rare (popmax 0.111%, sas); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Ile378Thr (c.1133T>C)?

MAP1B p.Ile378Thr (c.1133T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Ile378Thr (c.1133T>C) in the general population?

MAP1B p.Ile378Thr (c.1133T>C) is rare (popmax 0.111%, sas) (gnomAD).

What do computational predictors say about MAP1B p.Ile378Thr (c.1133T>C)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

MAP1B p.Ile378Thr

c.1133T>C · rs568808169 · VCV2399355

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.26, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	20.3	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 0.111% South Asian · 101/91,050 alleles

Filtering AF 0.0933% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0869%

Overall 0.00657% 106/1,614,036 alleles · rare exomes 99/1,461,780 · genomes 7/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.111%	901
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.000169%	590,016

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.Ile378Thr
Coding: c.1133T>C
MANE Select: NM_005909
dbSNP: rs568808169
Type: single nucleotide variant
Location: chr5:72194488 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 378: a UniProt-annotated variant site (in pvnh9)

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.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
MAP1B p.Lys1025Arg 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-ile378thr (accessed [today's date]).

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