Is MAP1B p.Arg1948Trp (c.5842C>T) pathogenic?

MAP1B p.Arg1948Trp (c.5842C>T) is classified Uncertain significance in MAP1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-12). AlphaMissense: likely benign (0.1823); Ultra-rare (popmax 0.056%, sas); Associated with hearing loss, autosomal dominant 83.

What condition is associated with MAP1B p.Arg1948Trp (c.5842C>T)?

MAP1B p.Arg1948Trp (c.5842C>T) is associated with hearing loss, autosomal dominant 83 (ClinVar).

How common is MAP1B p.Arg1948Trp (c.5842C>T) in the general population?

MAP1B p.Arg1948Trp (c.5842C>T) is ultra-rare (popmax 0.056%, sas) (gnomAD).

What do computational predictors say about MAP1B p.Arg1948Trp (c.5842C>T)?

AlphaMissense predicts likely benign (score 0.1823) — an in-silico prediction, not a clinical call.

MAP1B p.Arg1948Trp

c.5842C>T · VCV3377583

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss, autosomal dominant 83

Computational evidence

Protein change
AlphaMissense	0.1823	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -11.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.32	GERP -3.7, phastCons 0.009
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	22.2	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 0.056% South Asian · 51/91,070 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00403% 65/1,613,974 alleles · ultra-rare exomes 62/1,461,762 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Middle Eastern	0.033%	3,030
African / African-American	0.00267%	37,495
Admixed American	0.00167%	60,016
European (non-Finnish)	0.000763%	131,104

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.Arg1948Trp
Coding: c.5842C>T
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72199197 (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

hearing loss, autosomal dominant 83 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP1B p.Arg1948Gln Likely benign ★ same residue
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Lys2253Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Val1549Gly Uncertain significance ★★ ⚠ same condition
MAP1B p.Pro1634= Benign/Likely benign ★★ same condition
MAP1B p.Ser1731= Benign/Likely benign ★★ same condition
MAP1B p.Ala273Val Uncertain significance ★ ⚠ same condition
MAP1B p.Arg1897Trp 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-arg1948trp (accessed [today's date]).

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