Is MAP1B p.Ser1917Arg (c.5749A>C) pathogenic?

MAP1B p.Ser1917Arg (c.5749A>C) is classified Benign in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.1156); Low-frequency (popmax 4.77%, nfe); Associated with periventricular nodular heterotopia 9.

What condition is associated with MAP1B p.Ser1917Arg (c.5749A>C)?

MAP1B p.Ser1917Arg (c.5749A>C) is associated with periventricular nodular heterotopia 9 (ClinVar).

How common is MAP1B p.Ser1917Arg (c.5749A>C) in the general population?

MAP1B p.Ser1917Arg (c.5749A>C) is low-frequency (popmax 4.77%, nfe) (gnomAD).

What do computational predictors say about MAP1B p.Ser1917Arg (c.5749A>C)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

MAP1B p.Ser1917Arg

c.5749A>C · rs13153166 · VCV3068588

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.77%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

periventricular nodular heterotopia 9

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.16	GERP -4.2
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	6.529	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 4.77% European (non-Finnish) · 56,309/1,179,978 alleles

Filtering AF 4.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.73%

Overall 3.99% 64,342/1,614,098 alleles · low-frequency exomes 59,918/1,461,780 · genomes 4,424/152,318 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	4.77%	21
Finnishnot grpmax-eligible	3.96%	25
Remaining individualsnot grpmax-eligible	3.17%	32
Ashkenazi Jewishnot grpmax-eligible	2.27%	44
Admixed American	1.7%	59
South Asian	1.33%	75
Amishnot grpmax-eligible	1.1%	91
Middle Eastern	0.891%	112
African / African-American	0.724%	138
East Asian	0.0111%	8,978

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.Ser1917Arg
Coding: c.5749A>C
MANE Select: NM_005909
dbSNP: rs13153166
Type: single nucleotide variant
Location: chr5:72199104 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1917: a modified residue (phosphoserine); a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); a UniProt-annotated variant site (in); the 'disordered' region

Full MAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

periventricular nodular heterotopia 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Leu1453Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Lys2253Arg 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-ser1917arg (accessed [today's date]).

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