Is MAP1B p.Pro1182Arg (c.3545C>G) pathogenic?

MAP1B p.Pro1182Arg (c.3545C>G) is classified Uncertain significance in MAP1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-28). AlphaMissense: likely benign (0.0947); No allele count reported in gnomAD v4.1 (AN 1,614,180); Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Pro1182Arg (c.3545C>G)?

MAP1B p.Pro1182Arg (c.3545C>G) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Pro1182Arg (c.3545C>G) in the general population?

MAP1B p.Pro1182Arg (c.3545C>G) is no allele count reported in gnomAD v4.1 (AN 1,614,180) (gnomAD).

What do computational predictors say about MAP1B p.Pro1182Arg (c.3545C>G)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

MAP1B p.Pro1182Arg

c.3545C>G · rs779963708 · VCV2632754

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,180)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAP1B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.85	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	GERP 2.2, phastCons 0.83
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	17.23	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

No allele count reported in gnomAD v4.1 (AN 1,614,180). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAP1B
Protein: p.Pro1182Arg
Coding: c.3545C>G
MANE Select: NM_005909
dbSNP: rs779963708
Type: single nucleotide variant
Location: chr5:72196900 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1182: 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

MAP1B-related disorder

Similar variants

MAP1B p.Pro1182Leu Uncertain significance ★ ⚠ same residue
MAP1B p.Pro1182= Likely benign same residue
MAP1B p.Pro1182Thr Uncertain significance ★★ ⚠ same residue
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

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-pro1182arg (accessed [today's date]).

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