Is MAP1B p.Pro1634= (c.4902C>T) pathogenic?

MAP1B p.Pro1634= (c.4902C>T) is classified Benign/Likely benign in MAP1B (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-07-01). Rare (popmax 0.567%, nfe); Associated with hearing loss, autosomal dominant 83.

What condition is associated with MAP1B p.Pro1634= (c.4902C>T)?

MAP1B p.Pro1634= (c.4902C>T) is associated with hearing loss, autosomal dominant 83, periventricular nodular heterotopia 9 (ClinVar).

How common is MAP1B p.Pro1634= (c.4902C>T) in the general population?

MAP1B p.Pro1634= (c.4902C>T) is rare (popmax 0.567%, nfe) (gnomAD).

MAP1B p.Pro1634=

c.4902C>T · rs34984533 · VCV710322

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.567%, nfe)

Conditions

hearing loss, autosomal dominant 83

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 -1.8	GERP -4.3
Overall
CADD	6.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.567% European (non-Finnish) · 6,693/1,179,994 alleles

Filtering AF 0.556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.551%

Overall 0.475% 7,671/1,614,134 alleles · rare exomes 7,033/1,461,836 · genomes 638/152,298 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.567%	176
Admixed American	0.506%	197
Remaining individualsnot grpmax-eligible	0.435%	230
Finnishnot grpmax-eligible	0.267%	374
African / African-American	0.196%	511
Middle Eastern	0.132%	758
South Asian	0.0626%	1,598
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,645
East Asian	0.00223%	44,886

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.Pro1634=
Coding: c.4902C>T
MANE Select: NM_005909
dbSNP: rs34984533
Type: single nucleotide variant
Location: chr5:72198257 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1634: 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

Also linked: periventricular nodular heterotopia 9

Similar variants

MAP1B p.Pro1634Arg Likely benign ★ same residue
MAP1B p.Arg1664Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg303Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same condition
MAP1B p.Arg1399Cys Uncertain significance ★★ ⚠ same condition
MAP1B p.Arg1948Trp Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys 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-pro1634 (accessed [today's date]).

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