Is MAP1A p.Pro2064Arg (c.6191C>G) pathogenic?

MAP1A p.Pro2064Arg (c.6191C>G) is classified Uncertain significance in MAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: ambiguous (0.3408); Ultra-rare (popmax 0.0227%, afr).

How common is MAP1A p.Pro2064Arg (c.6191C>G) in the general population?

MAP1A p.Pro2064Arg (c.6191C>G) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about MAP1A p.Pro2064Arg (c.6191C>G)?

AlphaMissense predicts ambiguous (score 0.3408) — an in-silico prediction, not a clinical call.

MAP1A p.Pro2064Arg

c.6191C>G · VCV3869973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3408 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Computational evidence

Protein change
AlphaMissense	0.3408	ambiguous
REVEL	0.132	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	22.1	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 0.0227% African / African-American · 17/74,864 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00583% 94/1,613,412 alleles · ultra-rare exomes 83/1,461,612 · genomes 11/151,800 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,404
Admixed American	0.015%	6,662
Remaining individualsnot grpmax-eligible	0.0096%	10,414
South Asian	0.00549%	18,207
European (non-Finnish)	0.00466%	21,449
East Asian	0.00223%	44,828
Finnishnot grpmax-eligible	0.00156%	64,010

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.Pro2064Arg
Coding: c.6191C>G
MANE Select: NM_002373
Type: single nucleotide variant
Location: chr15:43527664 (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.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
MAP1A p.Ser1858Cys Likely 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-pro2064arg (accessed [today's date]).

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