Is MAP2 p.Asp176Asn (c.526G>A) pathogenic?

MAP2 p.Asp176Asn (c.526G>A) is classified Benign in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-31). AlphaMissense: likely benign (0.0758); Low-frequency (popmax 2.41%, sas).

How common is MAP2 p.Asp176Asn (c.526G>A) in the general population?

MAP2 p.Asp176Asn (c.526G>A) is low-frequency (popmax 2.41%, sas) (gnomAD).

What do computational predictors say about MAP2 p.Asp176Asn (c.526G>A)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

MAP2 p.Asp176Asn

c.526G>A · rs375849922 · VCV726279

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.41%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -7.34	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 8.5	GERP 2.6, phastCons 1
Overall
CADD	22.0	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 2.41% South Asian · 2,192/90,996 alleles

Filtering AF 2.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.29%

Overall 0.141% 2,271/1,613,678 alleles · low-frequency exomes 2,154/1,461,392 · genomes 117/152,286 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.41%	42
Middle Eastern	0.149%	673
Remaining individualsnot grpmax-eligible	0.0976%	1,024
African / African-American	0.00267%	37,498
East Asian	0.00223%	44,866
European (non-Finnish)	0.000509%	196,642

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.Asp176Asn
Coding: c.526G>A
MANE Select: NM_001375505
dbSNP: rs375849922
Type: single nucleotide variant
Location: chr2:209692696 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB
Residue 176: an α-helix

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-asp176asn (accessed [today's date]).

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