Is MAP1A p.Arg472His (c.1415G>A) pathogenic?

MAP1A p.Arg472His (c.1415G>A) is classified Uncertain significance in MAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.8404); Very rare (popmax 0.00551%, sas).

How common is MAP1A p.Arg472His (c.1415G>A) in the general population?

MAP1A p.Arg472His (c.1415G>A) is very rare (popmax 0.00551%, sas) (gnomAD).

What do computational predictors say about MAP1A p.Arg472His (c.1415G>A)?

AlphaMissense predicts likely pathogenic (score 0.8404) — an in-silico prediction, not a clinical call.

MAP1A p.Arg472His

c.1415G>A · VCV4102965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, sas)

Computational evidence

Protein change
AlphaMissense	0.8404	likely pathogenic
REVEL	0.349	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	29.6	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 0.00551% South Asian · 5/90,684 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00161% 26/1,611,650 alleles · very rare exomes 24/1,459,524 · genomes 2/152,126 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00551%	18,137
Admixed American	0.00336%	29,733
East Asian	0.00223%	44,838
European (non-Finnish)	0.00153%	65,492

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.Arg472His
Coding: c.1415G>A
MANE Select: NM_002373
Type: single nucleotide variant
Location: chr15:43522888 (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-arg472his (accessed [today's date]).

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