Is MAP2 p.Thr1154Ile (c.3461C>T) pathogenic?

MAP2 p.Thr1154Ile (c.3461C>T) is classified Uncertain significance in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.0708); Ultra-rare (popmax 0.0802%, sas).

How common is MAP2 p.Thr1154Ile (c.3461C>T) in the general population?

MAP2 p.Thr1154Ile (c.3461C>T) is ultra-rare (popmax 0.0802%, sas) (gnomAD).

What do computational predictors say about MAP2 p.Thr1154Ile (c.3461C>T)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

MAP2 p.Thr1154Ile

c.3461C>T · rs200843201 · VCV2466637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.21	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 -1.2	GERP -4.8
Overall
CADD	1.503	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 0.0802% South Asian · 73/91,074 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.00458% 74/1,614,064 alleles · ultra-rare exomes 70/1,461,830 · genomes 4/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0802%	1,248
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Thr1154Ile
Coding: c.3461C>T
MANE Select: NM_001375505
dbSNP: rs200843201
Type: single nucleotide variant
Location: chr2:209695631 (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.Thr1154Ala Uncertain significance ★ ⚠ same residue
MAP2 p.Thr1154= Likely benign ★ 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

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-thr1154ile (accessed [today's date]).

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