Is MAP2 p.Leu1762Val (c.5284T>G) pathogenic?

MAP2 p.Leu1762Val (c.5284T>G) is classified Uncertain significance in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: likely pathogenic (0.8139); Very rare (popmax 0.00153%, nfe).

How common is MAP2 p.Leu1762Val (c.5284T>G) in the general population?

MAP2 p.Leu1762Val (c.5284T>G) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about MAP2 p.Leu1762Val (c.5284T>G)?

AlphaMissense predicts likely pathogenic (score 0.8139) — an in-silico prediction, not a clinical call.

MAP2 p.Leu1762Val

c.5284T>G · VCV4051179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8139	likely pathogenic
REVEL	0.277	benign-leaning
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.93	GERP -0.63, phastCons 0.006
Overall
CADD	21.3	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 0.00153% European (non-Finnish) · 18/1,179,956 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00118% 19/1,613,838 alleles · very rare exomes 17/1,461,744 · genomes 2/152,094 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00153%	65,553
African / African-American	0.00134%	74,888

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: MAP2
Protein: p.Leu1762Val
Coding: c.5284T>G
MANE Select: NM_001375505
Type: single nucleotide variant
Location: chr2:209730197 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB

Full MAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2 p.Ala1074Thr Uncertain significance ★★ ⚠ same type
MAP2 p.Ala752Ser Uncertain significance ★★ ⚠ same type
MAP2 p.Arg1715His Uncertain significance ★★ ⚠ same type
MAP2 p.Val1359Ala Uncertain significance ★★ ⚠ same type
MAP2 p.Ala414Ser Benign/Likely benign ★★ same type
MAP2 p.Asp679= Benign ★★ same type
MAP2 p.Gln1760= Benign/Likely benign ★★ same type
MAP2 p.Glu1129= Benign ★★ same type

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/map2-p-leu1762val (accessed [today's date]).

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