Is MAP1B p.Lys623= (c.1869G>A) pathogenic?

MAP1B p.Lys623= (c.1869G>A) is classified Likely benign in MAP1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-03). Ultra-rare (popmax 0.076%, afr); Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Lys623= (c.1869G>A)?

MAP1B p.Lys623= (c.1869G>A) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Lys623= (c.1869G>A) in the general population?

MAP1B p.Lys623= (c.1869G>A) is ultra-rare (popmax 0.076%, afr) (gnomAD).

MAP1B p.Lys623=

c.1869G>A · rs112911289 · VCV3036062

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.076%, afr)

Conditions

MAP1B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.33, phastCons 1
Overall
CADD	6.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.076% African / African-American · 57/74,972 alleles

Filtering AF 0.0602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0545%

Overall 0.00428% 69/1,613,878 alleles · ultra-rare exomes 34/1,461,830 · genomes 35/152,048 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.076%	1,315
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.0011%	91,070

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.Lys623=
Coding: c.1869G>A
MANE Select: NM_005909
dbSNP: rs112911289
Type: single nucleotide variant
Location: chr5:72195224 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 623: 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

MAP1B-related disorder

Similar variants

MAP1B p.Lys623Glu Uncertain significance ★★ ⚠ same residue
MAP1B p.Pro1182Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Thr2194Met Uncertain significance ★★ ⚠ same condition
MAP1B p.Gln325Ter Likely pathogenic ★ same condition
MAP1B p.Lys751Ter Likely pathogenic ★ same condition
MAP1B p.Arg64Gln Uncertain significance ★ same condition
MAP1B p.Asp1637Asn Uncertain significance ★ ⚠ same condition
MAP1B p.Glu678Gly 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-lys623 (accessed [today's date]).

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