Is MAP1B p.Leu1750Pro (c.5249T>C) pathogenic?

MAP1B p.Leu1750Pro (c.5249T>C) is classified Likely benign in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-25). AlphaMissense: likely benign (0.1408); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Leu1750Pro (c.5249T>C)?

MAP1B p.Leu1750Pro (c.5249T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Leu1750Pro (c.5249T>C) in the general population?

MAP1B p.Leu1750Pro (c.5249T>C) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about MAP1B p.Leu1750Pro (c.5249T>C)?

AlphaMissense predicts likely benign (score 0.1408) — an in-silico prediction, not a clinical call.

MAP1B p.Leu1750Pro

c.5249T>C · VCV3542614

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1408	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.41	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 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	23.2	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 0.00144% European (non-Finnish) · 17/1,180,048 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,614,068 alleles · very rare exomes 13/1,461,870 · genomes 4/152,198 · 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: MAP1B
Protein: p.Leu1750Pro
Coding: c.5249T>C
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72198604 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1750: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); the 'disordered' region

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-leu1750pro (accessed [today's date]).

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