Is MAP2 p.Val407Phe (c.1219G>T) pathogenic?

MAP2 p.Val407Phe (c.1219G>T) is classified Benign in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0861); Low-frequency (popmax 1.34%, afr).

How common is MAP2 p.Val407Phe (c.1219G>T) in the general population?

MAP2 p.Val407Phe (c.1219G>T) is low-frequency (popmax 1.34%, afr) (gnomAD).

What do computational predictors say about MAP2 p.Val407Phe (c.1219G>T)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

MAP2 p.Val407Phe

c.1219G>T · rs755708 · VCV791122

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.30	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 1.4	GERP -0.18, phastCons 0.001
Overall
CADD	11.47	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 1.34% African / African-American · 1,003/74,728 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0722% 1,164/1,612,078 alleles · low-frequency exomes 561/1,459,824 · genomes 603/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.34%	75
Middle Eastern	0.116%	863
Remaining individualsnot grpmax-eligible	0.109%	918
Admixed American	0.101%	993
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,837
South Asian	0.00663%	15,081
European (non-Finnish)	0.00144%	69,388

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.Val407Phe
Coding: c.1219G>T
MANE Select: NM_001375505
dbSNP: rs755708
Type: single nucleotide variant
Location: chr2:209693389 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB
Residue 407: an α-helix

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

Similar variants

METAP2 p.Asn407Ser 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-val407phe (accessed [today's date]).

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