Is MAP2 p.Glu55Lys (c.163G>A) pathogenic?

MAP2 p.Glu55Lys (c.163G>A) is classified Benign/Likely benign in MAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.1113); Low-frequency (popmax 1.54%, nfe).

How common is MAP2 p.Glu55Lys (c.163G>A) in the general population?

MAP2 p.Glu55Lys (c.163G>A) is low-frequency (popmax 1.54%, nfe) (gnomAD).

What do computational predictors say about MAP2 p.Glu55Lys (c.163G>A)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

MAP2 p.Glu55Lys

c.163G>A · rs139310749 · VCV774414

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	27.4	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 1.54% European (non-Finnish) · 18,195/1,179,990 alleles

Filtering AF 1.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.52%

Overall 1.28% 20,603/1,614,150 alleles · low-frequency exomes 19,208/1,461,820 · genomes 1,395/152,330 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.87%	54
European (non-Finnish)grpmax	1.54%	65
Middle Eastern	1.11%	90
Remaining individualsnot grpmax-eligible	1.05%	95
Ashkenazi Jewishnot grpmax-eligible	0.905%	110
Finnishnot grpmax-eligible	0.895%	112
South Asian	0.424%	236
Admixed American	0.382%	262
African / African-American	0.282%	354

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu55Lys
Coding: c.163G>A
MANE Select: NM_001375505
dbSNP: rs139310749
Type: single nucleotide variant
Location: chr2:209653333 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB
Residue 55: the 'disordered' region

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-glu55lys (accessed [today's date]).

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