Is MAP2 p.Leu153Ser (c.458T>C) pathogenic?

MAP2 p.Leu153Ser (c.458T>C) is classified Uncertain significance in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.2569); Very rare (popmax 0.00601%, sas).

How common is MAP2 p.Leu153Ser (c.458T>C) in the general population?

MAP2 p.Leu153Ser (c.458T>C) is very rare (popmax 0.00601%, sas) (gnomAD).

What do computational predictors say about MAP2 p.Leu153Ser (c.458T>C)?

AlphaMissense predicts likely benign (score 0.2569) — an in-silico prediction, not a clinical call.

MAP2 p.Leu153Ser

c.458T>C · VCV4549323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00601%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2569	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Overall
CADD	25.7	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 0.00601% South Asian · 5/83,144 alleles

Filtering AF 0.00236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00148%

Overall 0.00247% 35/1,415,060 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00601%	16,629
Remaining individualsnot grpmax-eligible	0.00497%	20,119
European (non-Finnish)	0.00232%	43,066

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.Leu153Ser
Coding: c.458T>C
MANE Select: NM_006838 · reported on NM_001375505
Type: single nucleotide variant
Location: chr2:209692628 (GRCh38)
Structure: AlphaFold pLDDT 86.07 · 40 PDB
Residue 153: 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-leu153ser (accessed [today's date]).

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