Is MAP2 p.Arg1551Gln (c.4652G>A) pathogenic?

MAP2 p.Arg1551Gln (c.4652G>A) is classified Uncertain significance in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: ambiguous (0.4189); Very rare (popmax 0.000509%, nfe).

How common is MAP2 p.Arg1551Gln (c.4652G>A) in the general population?

MAP2 p.Arg1551Gln (c.4652G>A) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about MAP2 p.Arg1551Gln (c.4652G>A)?

AlphaMissense predicts ambiguous (score 0.4189) — an in-silico prediction, not a clinical call.

MAP2 p.Arg1551Gln

c.4652G>A · rs775158582 · VCV2490957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4189	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Overall
CADD	33.0	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 0.000509% European (non-Finnish) · 6/1,179,448 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,090 alleles · very rare exomes 5/1,461,048 · genomes 1/152,042 · joint denominator

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.Arg1551Gln
Coding: c.4652G>A
MANE Select: NM_001375505
dbSNP: rs775158582
Type: single nucleotide variant
Location: chr2:209705647 (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.Arg1551Trp Uncertain significance ★ ⚠ same residue
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

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-arg1551gln (accessed [today's date]).

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