Is MAP2 p.Arg5Trp (c.13C>T) pathogenic?

MAP2 p.Arg5Trp (c.13C>T) is classified Uncertain significance in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely pathogenic (0.565); Ultra-rare (popmax 0.0337%, mid).

How common is MAP2 p.Arg5Trp (c.13C>T) in the general population?

MAP2 p.Arg5Trp (c.13C>T) is ultra-rare (popmax 0.0337%, mid) (gnomAD).

What do computational predictors say about MAP2 p.Arg5Trp (c.13C>T)?

AlphaMissense predicts likely pathogenic (score 0.565) — an in-silico prediction, not a clinical call.

MAP2 p.Arg5Trp

c.13C>T · rs138782038 · VCV2217066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.565	likely pathogenic
REVEL	0.186	benign-leaning
SaProt	LLR -8.63	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 3.2	GERP 1.1, phastCons 1
Overall
CADD	28.1	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 0.0337% Middle Eastern · 2/5,928 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00295% 47/1,595,638 alleles · ultra-rare exomes 43/1,443,404 · genomes 4/152,234 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0337%	2,964
European (non-Finnish)	0.00333%	30,071
Remaining individualsnot grpmax-eligible	0.00324%	30,817
East Asian	0.00224%	44,594
Finnishnot grpmax-eligible	0.00157%	63,638
African / African-American	0.00135%	74,226
South Asian	0.00114%	87,826

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.Arg5Trp
Coding: c.13C>T
MANE Select: NM_001375505
dbSNP: rs138782038
Type: single nucleotide variant
Location: chr2:209653183 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB
Residue 5: the 'disordered' region

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

Similar variants

MAP2 p.Arg5Gln 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-arg5trp (accessed [today's date]).

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