Is MAP1B p.Pro1182Thr (c.3544C>A) pathogenic?

MAP1B p.Pro1182Thr (c.3544C>A) is classified Uncertain significance in MAP1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-23). AlphaMissense: likely benign (0.0546); Very rare (popmax 0.00878%, sas); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Pro1182Thr (c.3544C>A)?

MAP1B p.Pro1182Thr (c.3544C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Pro1182Thr (c.3544C>A) in the general population?

MAP1B p.Pro1182Thr (c.3544C>A) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about MAP1B p.Pro1182Thr (c.3544C>A)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

MAP1B p.Pro1182Thr

c.3544C>A · rs571066866 · VCV2495251

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.09	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 -0.021	GERP -4.4, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	3.478	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

Grpmax group 0.00878% South Asian · 8/91,074 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000558% 9/1,614,208 alleles · very rare exomes 8/1,461,868 · genomes 1/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Pro1182Thr
Coding: c.3544C>A
MANE Select: NM_005909
dbSNP: rs571066866
Type: single nucleotide variant
Location: chr5:72196899 (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

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

Similar variants

MAP1B p.Pro1182Arg Uncertain significance ★★ ⚠ same residue
MAP1B p.Pro1182Leu Uncertain significance ★ ⚠ same residue
MAP1B p.Pro1182= Likely benign 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

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-pro1182thr (accessed [today's date]).

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