Is MAP1B p.Pro1357Ser (c.4069C>T) pathogenic?

MAP1B p.Pro1357Ser (c.4069C>T) is classified Likely benign in MAP1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely benign (0.0603); Rare (popmax 0.312%, eas); Associated with MAP1B-related disorder.

What condition is associated with MAP1B p.Pro1357Ser (c.4069C>T)?

MAP1B p.Pro1357Ser (c.4069C>T) is associated with MAP1B-related disorder (ClinVar).

How common is MAP1B p.Pro1357Ser (c.4069C>T) in the general population?

MAP1B p.Pro1357Ser (c.4069C>T) is rare (popmax 0.312%, eas) (gnomAD).

What do computational predictors say about MAP1B p.Pro1357Ser (c.4069C>T)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

MAP1B p.Pro1357Ser

c.4069C>T · rs147375647 · VCV3054249

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.312%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MAP1B-related disorder

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.47	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 0.34	GERP -4.5, phastCons 0.002
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	7.058	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 0.312% East Asian · 140/44,880 alleles

Filtering AF 0.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.00886% 143/1,614,206 alleles · rare exomes 131/1,461,884 · genomes 12/152,322 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.312%	321
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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.Pro1357Ser
Coding: c.4069C>T
MANE Select: NM_005909
dbSNP: rs147375647
Type: single nucleotide variant
Location: chr5:72197424 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1357: 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-pro1357ser (accessed [today's date]).

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