Is MAP1B p.Gly1990Arg (c.5968G>C) pathogenic?

MAP1B p.Gly1990Arg (c.5968G>C) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: ambiguous (0.5083); Absent from gnomAD v4.1.

How common is MAP1B p.Gly1990Arg (c.5968G>C) in the general population?

MAP1B p.Gly1990Arg (c.5968G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP1B p.Gly1990Arg (c.5968G>C)?

AlphaMissense predicts ambiguous (score 0.5083) — an in-silico prediction, not a clinical call.

MAP1B p.Gly1990Arg

c.5968G>C · rs1747267543 · VCV2500458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5083 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5083	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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.Gly1990Arg
Coding: c.5968G>C
MANE Select: NM_005909
dbSNP: rs1747267543
Type: single nucleotide variant
Location: chr5:72199323 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1990: 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

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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-gly1990arg (accessed [today's date]).

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