Is MAP1B p.Lys663fs (c.1988del) pathogenic?

MAP1B p.Lys663fs (c.1988del) is classified Pathogenic in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). Very rare (popmax 8.52e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Lys663fs (c.1988del)?

MAP1B p.Lys663fs (c.1988del) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Lys663fs (c.1988del) in the general population?

MAP1B p.Lys663fs (c.1988del) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

MAP1B p.Lys663fs

c.1988del · rs2478570422 · VCV2603792

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.091	GERP -4.3, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,174,116 alleles

Overall 6.26e-05% 1/1,596,936 alleles · very rare exomes 1/1,449,390 · genomes 0/147,546 · 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.Lys663fs
Coding: c.1988del
MANE Select: NM_005909
dbSNP: rs2478570422
Type: Deletion
Location: chr5:72195339 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 663: the 'disordered' region; a UniProt-annotated variant site (in pvnh9)

Full MAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP1B p.Tyr2023fs Pathogenic ★ same condition
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1480Tyr Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1993Gly Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu2435Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly919Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly932Ser 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-lys663fs (accessed [today's date]).

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