Is MAP2 p.His976Leu (c.2927A>T) pathogenic?

MAP2 p.His976Leu (c.2927A>T) is classified Benign in MAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0713); Low-frequency (popmax 4.61%, afr).

How common is MAP2 p.His976Leu (c.2927A>T) in the general population?

MAP2 p.His976Leu (c.2927A>T) is low-frequency (popmax 4.61%, afr) (gnomAD).

What do computational predictors say about MAP2 p.His976Leu (c.2927A>T)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

MAP2 p.His976Leu

c.2927A>T · rs13425372 · VCV779081

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.61%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -4.41	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 1.5	GERP 0.048
Overall
CADD	5.72	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 4.61% African / African-American · 3,458/75,048 alleles

Filtering AF 4.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.43%

Overall 0.238% 3,842/1,614,184 alleles · low-frequency exomes 1,929/1,461,862 · genomes 1,913/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.61%	22
Remaining individualsnot grpmax-eligible	0.237%	422
Admixed American	0.233%	429
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.0072%	13,883
South Asian	0.00549%	18,216

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.His976Leu
Coding: c.2927A>T
MANE Select: NM_001375505
dbSNP: rs13425372
Type: single nucleotide variant
Location: chr2:209695097 (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.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-his976leu (accessed [today's date]).

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