Is MAP2 p.Lys1344Thr (c.4031A>C) pathogenic?

MAP2 p.Lys1344Thr (c.4031A>C) is classified Likely benign in MAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-17). AlphaMissense: likely benign (0.2338); Rare (popmax 0.737%, afr).

How common is MAP2 p.Lys1344Thr (c.4031A>C) in the general population?

MAP2 p.Lys1344Thr (c.4031A>C) is rare (popmax 0.737%, afr) (gnomAD).

What do computational predictors say about MAP2 p.Lys1344Thr (c.4031A>C)?

AlphaMissense predicts likely benign (score 0.2338) — an in-silico prediction, not a clinical call.

MAP2 p.Lys1344Thr

c.4031A>C · rs35915945 · VCV734114

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2338 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.737%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2338	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.42	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 -4.7, phastCons 1
Overall
CADD	14.98	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 0.737% African / African-American · 553/74,988 alleles

Filtering AF 0.687% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.666%

Overall 0.0371% 599/1,613,750 alleles · rare exomes 308/1,461,538 · genomes 291/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.737%	136
Middle Eastern	0.0825%	1,212
Admixed American	0.0384%	2,606
Remaining individualsnot grpmax-eligible	0.0288%	3,471

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.Lys1344Thr
Coding: c.4031A>C
MANE Select: NM_001375505
dbSNP: rs35915945
Type: single nucleotide variant
Location: chr2:209696201 (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-lys1344thr (accessed [today's date]).

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