Is MAP2 p.Arg1715His (c.5144G>A) pathogenic?

MAP2 p.Arg1715His (c.5144G>A) is classified Uncertain significance in MAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-12). AlphaMissense: likely benign (0.1201); Very rare (popmax 0.00354%, amr).

How common is MAP2 p.Arg1715His (c.5144G>A) in the general population?

MAP2 p.Arg1715His (c.5144G>A) is very rare (popmax 0.00354%, amr) (gnomAD).

What do computational predictors say about MAP2 p.Arg1715His (c.5144G>A)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

MAP2 p.Arg1715His

c.5144G>A · rs1166578294 · VCV1342570

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00354%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -0.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00354% Admixed American · 2/56,500 alleles

Filtering AF 0.000962% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000794%

Overall 0.00151% 24/1,592,738 alleles · very rare exomes 24/1,440,462 · genomes 0/152,276 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00354%	28,250
African / African-American	0.0027%	37,034
Finnishnot grpmax-eligible	0.00157%	63,812
European (non-Finnish)	0.00154%	64,957
South Asian	0.00114%	87,358

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.Arg1715His
Coding: c.5144G>A
MANE Select: NM_001375505
dbSNP: rs1166578294
Type: single nucleotide variant
Location: chr2:209725779 (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.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
MAP2 p.Glu179Gly 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-arg1715his (accessed [today's date]).

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