Is MAP2 p.Pro18= (c.54G>A) pathogenic?

MAP2 p.Pro18= (c.54G>A) is classified Likely benign in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-10). Very rare (popmax 0.00989%, sas).

How common is MAP2 p.Pro18= (c.54G>A) in the general population?

MAP2 p.Pro18= (c.54G>A) is very rare (popmax 0.00989%, sas) (gnomAD).

MAP2 p.Pro18=

c.54G>A · rs754431951 · VCV792326

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -3.9
Overall
CADD	8.905	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00989% South Asian · 9/91,042 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00601% 97/1,613,710 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,942
South Asiangrpmax	0.00989%	10,116
African / African-American	0.00667%	14,982
European (non-Finnish)	0.0061%	16,387
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,576
Admixed American	0.00167%	59,918

Remaining individuals 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.Pro18=
Coding: c.54G>A
MANE Select: NM_006838 · reported on NM_001375505
dbSNP: rs754431951
Type: single nucleotide variant
Location: chr2:209653224 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB
Residue 18: the 'disordered' region

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

Similar variants

MAP2 p.Pro18Leu 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-pro18 (accessed [today's date]).

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