Is MAP1B p.Lys1908= (c.5724G>A) pathogenic?

MAP1B p.Lys1908= (c.5724G>A) is classified Benign in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). Common (popmax 18.3%, mid) — too common for a highly-penetrant pathogenic allele.

MAP1B p.Lys1908=

Q: How common is MAP1B p.Lys1908= (c.5724G>A) in the general population?

MAP1B p.Lys1908= (c.5724G>A) is common (popmax 18.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5724G>A · VCV4970718

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18.3%, mid) — too common for a highly-penetrant pathogenic allele

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 7.6	GERP -0.82, phastCons 1
Overall
CADD	5.689	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.3% Middle Eastern · 1,111/6,062 alleles

Filtering AF 17.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.1%

Overall 11.3% 181,672/1,613,902 alleles · common exomes 165,360/1,461,758 · genomes 16,312/152,144 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	27.6%	4
Middle Easterngrpmax	18.3%	5
Ashkenazi Jewishnot grpmax-eligible	17.6%	6
European (non-Finnish)	11.7%	9
Remaining individualsnot grpmax-eligible	11.5%	9
South Asian	11.1%	9
Finnishnot grpmax-eligible	10.8%	9
African / African-American	10.6%	9
Admixed American	6.33%	16
East Asian	3.21%	31

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys1908=
Coding: c.5724G>A
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72199079 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1908: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression)

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

Similar variants

MAP1B p.Arg1664Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg2140Ter Pathogenic ★★ same type
MAP1B p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg85Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same type
MAP1B p.Arg1399Cys Uncertain significance ★★ ⚠ same type
MAP1B p.Arg1948Trp Uncertain significance ★★ ⚠ same type

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-lys1908 (accessed [today's date]).

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