Is MAP1B p.Arg2399Gln (c.7196G>A) pathogenic?

MAP1B p.Arg2399Gln (c.7196G>A) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). AlphaMissense: ambiguous (0.3788); Very rare (popmax 0.00167%, amr).

How common is MAP1B p.Arg2399Gln (c.7196G>A) in the general population?

MAP1B p.Arg2399Gln (c.7196G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MAP1B p.Arg2399Gln (c.7196G>A)?

AlphaMissense predicts ambiguous (score 0.3788) — an in-silico prediction, not a clinical call.

MAP1B p.Arg2399Gln

c.7196G>A · VCV4822535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.3788	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -9.26	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 5,431 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	28.1	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

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,484 alleles · very rare exomes 5/1,461,188 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
African / African-American	0.00133%	75,010
European (non-Finnish)	0.000254%	393,340

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.Arg2399Gln
Coding: c.7196G>A
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72203746 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 2399: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); the 'mediates interaction with tmem185a' region

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-arg2399gln (accessed [today's date]).

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