Is MAP1B p.Ile1391Val (c.4171A>G) pathogenic?

MAP1B p.Ile1391Val (c.4171A>G) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-28). AlphaMissense: likely benign (0.0782); Very rare (popmax 0.000593%, nfe); Associated with periventricular nodular heterotopia 9.

What condition is associated with MAP1B p.Ile1391Val (c.4171A>G)?

MAP1B p.Ile1391Val (c.4171A>G) is associated with periventricular nodular heterotopia 9, hearing loss, autosomal dominant 83 (ClinVar).

How common is MAP1B p.Ile1391Val (c.4171A>G) in the general population?

MAP1B p.Ile1391Val (c.4171A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about MAP1B p.Ile1391Val (c.4171A>G)?

AlphaMissense predicts likely benign (score 0.0782) — an in-silico prediction, not a clinical call.

MAP1B p.Ile1391Val

c.4171A>G · VCV3891619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

periventricular nodular heterotopia 9

Computational evidence

Protein change
AlphaMissense	0.0782	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -5.31	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 4.1	GERP -0.11, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	15.14	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 0.000593% European (non-Finnish) · 7/1,180,040 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,614,058 alleles · very rare exomes 7/1,461,868 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.000593%	168,577

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile1391Val
Coding: c.4171A>G
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72197526 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1391: 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

Also linked: hearing loss, autosomal dominant 83

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.Arg1948Trp Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Leu1453Val 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-ile1391val (accessed [today's date]).

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