Is MAP1B p.Glu2108Asp (c.6324G>C) pathogenic?

MAP1B p.Glu2108Asp (c.6324G>C) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-26). AlphaMissense: likely benign (0.3055); Very rare (popmax 0.00267%, afr); Associated with periventricular nodular heterotopia 9.

What condition is associated with MAP1B p.Glu2108Asp (c.6324G>C)?

MAP1B p.Glu2108Asp (c.6324G>C) is associated with periventricular nodular heterotopia 9 (ClinVar).

How common is MAP1B p.Glu2108Asp (c.6324G>C) in the general population?

MAP1B p.Glu2108Asp (c.6324G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MAP1B p.Glu2108Asp (c.6324G>C)?

AlphaMissense predicts likely benign (score 0.3055) — an in-silico prediction, not a clinical call.

MAP1B p.Glu2108Asp

c.6324G>C · rs888037943 · VCV1701651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

periventricular nodular heterotopia 9

Computational evidence

Protein change
AlphaMissense	0.3055	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.16	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 2.9	GERP 0.59, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	20.6	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 0.00267% African / African-American · 2/75,040 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,146 alleles · very rare exomes 2/1,461,890 · genomes 0/152,256 · 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.Glu2108Asp
Coding: c.6324G>C
MANE Select: NM_005909
dbSNP: rs888037943
Type: single nucleotide variant
Location: chr5:72199679 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 2108: 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

periventricular nodular heterotopia 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP1B p.Arg1664Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg303Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg1399Cys Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Leu1453Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Lys2253Arg 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-glu2108asp (accessed [today's date]).

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