Is MAP1A p.Arg2445Cys (c.7333C>T) pathogenic?

MAP1A p.Arg2445Cys (c.7333C>T) is classified Likely benign in MAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-29). AlphaMissense: likely benign (0.0762); Rare (popmax 0.132%, nfe).

How common is MAP1A p.Arg2445Cys (c.7333C>T) in the general population?

MAP1A p.Arg2445Cys (c.7333C>T) is rare (popmax 0.132%, nfe) (gnomAD).

What do computational predictors say about MAP1A p.Arg2445Cys (c.7333C>T)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

MAP1A p.Arg2445Cys

c.7333C>T · rs199715888 · VCV2286859

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -2.2
Overall
CADD	8.509	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% European (non-Finnish) · 1,558/1,179,950 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.105% 1,688/1,613,504 alleles · rare exomes 1,584/1,461,254 · genomes 104/152,250 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.132%	757
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0928%	1,078
South Asian	0.0362%	2,759
African / African-American	0.0227%	4,413
Admixed American	0.0133%	7,500
Finnishnot grpmax-eligible	0.0126%	7,945

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: MAP1A
Protein: p.Arg2445Cys
Coding: c.7333C>T
MANE Select: NM_002373
dbSNP: rs199715888
Type: single nucleotide variant
Location: chr15:43528806 (GRCh38)
Structure: AlphaFold pLDDT 94.44 · 41 PDB

Full MAP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP1A p.Arg2445Leu Uncertain significance ★ ⚠ same residue
MAP1A p.Arg2734Gln Uncertain significance ★★ same type
MAP1A p.Gly567Ala Uncertain significance ★★ ⚠ same type
MAP1A p.Gly482= Benign/Likely benign ★★ same type
MAP1A p.Leu1621Val Benign ★★ same type
MAP1A p.Ser1152= Likely benign ★★ same type
MAP1A p.Ser1311= Benign/Likely benign ★★ same type
MAP1A p.Ser1544= 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/map1a-p-arg2445cys (accessed [today's date]).

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