Is MAP1B p.Arg1948Gln (c.5843G>A) pathogenic?

MAP1B p.Arg1948Gln (c.5843G>A) is classified Likely benign in MAP1B (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1018); Ultra-rare (popmax 0.066%, mid); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Arg1948Gln (c.5843G>A)?

MAP1B p.Arg1948Gln (c.5843G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Arg1948Gln (c.5843G>A) in the general population?

MAP1B p.Arg1948Gln (c.5843G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about MAP1B p.Arg1948Gln (c.5843G>A)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

MAP1B p.Arg1948Gln

c.5843G>A · rs139240427 · VCV3054462

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -9.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.25, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	21.9	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 0.066% Middle Eastern · 4/6,060 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00397% 64/1,613,962 alleles · ultra-rare exomes 39/1,461,780 · genomes 25/152,182 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,515
African / African-American	0.0347%	2,884
South Asian	0.0121%	8,279
Admixed American	0.00667%	14,999
Remaining individualsnot grpmax-eligible	0.0032%	31,251
Finnishnot grpmax-eligible	0.00156%	64,006
European (non-Finnish)	0.00136%	73,746

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.Arg1948Gln
Coding: c.5843G>A
MANE Select: NM_005909
dbSNP: rs139240427
Type: single nucleotide variant
Location: chr5:72199198 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1948: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); the 'disordered' region

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.Arg1948Trp Uncertain significance ★★ ⚠ same residue
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-arg1948gln (accessed [today's date]).

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