Is MAP1B p.Pro1264Gln (c.3791C>A) pathogenic?

MAP1B p.Pro1264Gln (c.3791C>A) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely benign (0.1369); Very rare (popmax 0.00333%, amr); Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Pro1264Gln (c.3791C>A)?

MAP1B p.Pro1264Gln (c.3791C>A) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Pro1264Gln (c.3791C>A) in the general population?

MAP1B p.Pro1264Gln (c.3791C>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MAP1B p.Pro1264Gln (c.3791C>A)?

AlphaMissense predicts likely benign (score 0.1369) — an in-silico prediction, not a clinical call.

MAP1B p.Pro1264Gln

c.3791C>A · rs777278694 · VCV2633771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAP1B-related disorder

Computational evidence

Protein change
AlphaMissense	0.1369	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.58	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 1.3	GERP 1.2, phastCons 0.2
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000248% 4/1,614,114 alleles · very rare exomes 3/1,461,886 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,090

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.Pro1264Gln
Coding: c.3791C>A
MANE Select: NM_005909
dbSNP: rs777278694
Type: single nucleotide variant
Location: chr5:72197146 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1264: 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

MAP1B-related disorder

Similar variants

MAP1B p.Pro1182Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Thr2194Met Uncertain significance ★★ ⚠ same condition
MAP1B p.Gln325Ter Likely pathogenic ★ same condition
MAP1B p.Lys751Ter Likely pathogenic ★ same condition
MAP1B p.Arg64Gln Uncertain significance ★ same condition
MAP1B p.Asp1637Asn Uncertain significance ★ ⚠ same condition
MAP1B p.Glu678Gly Uncertain significance ★ ⚠ same condition
MAP1B p.Glu927Asp 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-pro1264gln (accessed [today's date]).

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