Is MAP1B p.Ala22= (c.66G>A) pathogenic?

MAP1B p.Ala22= (c.66G>A) is classified Likely benign in MAP1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Rare (popmax 0.131%, nfe); Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Ala22= (c.66G>A)?

MAP1B p.Ala22= (c.66G>A) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Ala22= (c.66G>A) in the general population?

MAP1B p.Ala22= (c.66G>A) is rare (popmax 0.131%, nfe) (gnomAD).

MAP1B p.Ala22=

c.66G>A · rs372802132 · VCV3046013

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.131%, nfe)

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 -0.078	GERP -6.2, phastCons 0.1
Overall
CADD	5.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% European (non-Finnish) · 1,541/1,177,010 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.102% 1,626/1,594,928 alleles · rare exomes 1,524/1,442,598 · genomes 102/152,330 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.131%	764
Remaining individualsnot grpmax-eligible	0.0596%	1,677
Finnishnot grpmax-eligible	0.0453%	2,207
Ashkenazi Jewishnot grpmax-eligible	0.0272%	3,678
African / African-American	0.0187%	5,347
Admixed American	0.00505%	19,791

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.Ala22=
Coding: c.66G>A
MANE Select: NM_005909
dbSNP: rs372802132
Type: single nucleotide variant
Location: chr5:72107597 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 22: the 'disordered' region

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

Disease context

MAP1B-related disorder

Similar variants

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
MAP1B p.Glu927Asp 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-ala22 (accessed [today's date]).

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