Is MAP2 p.Pro1007Thr (c.3019C>A) pathogenic?

MAP2 p.Pro1007Thr (c.3019C>A) is classified Uncertain significance in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely benign (0.055); Ultra-rare (popmax 0.0257%, nfe).

How common is MAP2 p.Pro1007Thr (c.3019C>A) in the general population?

MAP2 p.Pro1007Thr (c.3019C>A) is ultra-rare (popmax 0.0257%, nfe) (gnomAD).

What do computational predictors say about MAP2 p.Pro1007Thr (c.3019C>A)?

AlphaMissense predicts likely benign (score 0.055) — an in-silico prediction, not a clinical call.

MAP2 p.Pro1007Thr

c.3019C>A · VCV3870070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0257%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.055	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.53	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 -0.072	GERP -5
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0257% European (non-Finnish) · 303/1,180,010 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.0192% 310/1,613,966 alleles · ultra-rare exomes 298/1,461,856 · genomes 12/152,110 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0257%	3,894
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Finnishnot grpmax-eligible	0.00312%	32,006
South Asian	0.0011%	91,088

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.Pro1007Thr
Coding: c.3019C>A
MANE Select: NM_001375505
Type: single nucleotide variant
Location: chr2:209695189 (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
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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-pro1007thr (accessed [today's date]).

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