Is MAP1B p.Pro2131= (c.6393G>A) pathogenic?

MAP1B p.Pro2131= (c.6393G>A) is classified Likely benign in MAP1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-05). Rare (popmax 0.143%, eas); Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Pro2131= (c.6393G>A)?

MAP1B p.Pro2131= (c.6393G>A) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Pro2131= (c.6393G>A) in the general population?

MAP1B p.Pro2131= (c.6393G>A) is rare (popmax 0.143%, eas) (gnomAD).

MAP1B p.Pro2131=

c.6393G>A · rs149330290 · VCV3035157

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.143%, eas)

Conditions

MAP1B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.9
Overall
CADD	0.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.143% East Asian · 64/44,894 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.00799% 129/1,613,980 alleles · rare exomes 116/1,461,886 · genomes 13/152,094 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.143%	701
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.00534%	18,724
European (non-Finnish)	0.00441%	22,693
Admixed American	0.00167%	60,004
South Asian	0.0011%	91,076

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.Pro2131=
Coding: c.6393G>A
MANE Select: NM_005909
dbSNP: rs149330290
Type: single nucleotide variant
Location: chr5:72199748 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 2131: 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.Pro1182Arg Uncertain significance ★★ ⚠ same condition
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
MAP1B p.Glu678Gly Uncertain significance ★ ⚠ same condition
MAP1B p.Glu927Asp 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-pro2131 (accessed [today's date]).

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