Is MAP1B p.Ala1245Asp (c.3734C>A) pathogenic?

MAP1B p.Ala1245Asp (c.3734C>A) is classified Likely benign in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1045); Ultra-rare (popmax 0.0397%, nfe).

How common is MAP1B p.Ala1245Asp (c.3734C>A) in the general population?

MAP1B p.Ala1245Asp (c.3734C>A) is ultra-rare (popmax 0.0397%, nfe) (gnomAD).

What do computational predictors say about MAP1B p.Ala1245Asp (c.3734C>A)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

MAP1B p.Ala1245Asp

c.3734C>A · VCV4281064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0397%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.60	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 0.011	GERP 0.58
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	9.136	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 0.0397% European (non-Finnish) · 469/1,180,034 alleles

Filtering AF 0.0367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0355%

Overall 0.0304% 490/1,614,228 alleles · ultra-rare exomes 461/1,461,890 · genomes 29/152,338 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0397%	2,516
Remaining individualsnot grpmax-eligible	0.0272%	3,677
African / African-American	0.00533%	18,767

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.Ala1245Asp
Coding: c.3734C>A
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72197089 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1245: 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

Similar variants

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MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same type
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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-ala1245asp (accessed [today's date]).

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