Is MAP1B p.Pro248Thr (c.742C>A) pathogenic?

MAP1B p.Pro248Thr (c.742C>A) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-30). AlphaMissense: likely pathogenic (0.9241); Absent from gnomAD v4.1; Associated with periventricular nodular heterotopia 9.

What condition is associated with MAP1B p.Pro248Thr (c.742C>A)?

MAP1B p.Pro248Thr (c.742C>A) is associated with periventricular nodular heterotopia 9 (ClinVar).

How common is MAP1B p.Pro248Thr (c.742C>A) in the general population?

MAP1B p.Pro248Thr (c.742C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP1B p.Pro248Thr (c.742C>A)?

AlphaMissense predicts likely pathogenic (score 0.9241) — an in-silico prediction, not a clinical call.

MAP1B p.Pro248Thr

c.742C>A · rs1747089370 · VCV1027647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9241 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

periventricular nodular heterotopia 9

Computational evidence

Protein change
AlphaMissense	0.9241	likely pathogenic
REVEL	0.396	indeterminate
SaProt	LLR -11.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 87 kb · p 3.4e-10 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP1B
Protein: p.Pro248Thr
Coding: c.742C>A
MANE Select: NM_005909
dbSNP: rs1747089370
Type: single nucleotide variant
Location: chr5:72194097 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18

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-pro248thr (accessed [today's date]).

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