Is MAP1A p.Pro2516Arg (c.7547C>G) pathogenic?

MAP1A p.Pro2516Arg (c.7547C>G) is classified Uncertain significance in MAP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely pathogenic (0.9486); Very rare (popmax 0.000169%, nfe).

How common is MAP1A p.Pro2516Arg (c.7547C>G) in the general population?

MAP1A p.Pro2516Arg (c.7547C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about MAP1A p.Pro2516Arg (c.7547C>G)?

AlphaMissense predicts likely pathogenic (score 0.9486) — an in-silico prediction, not a clinical call.

MAP1A p.Pro2516Arg

c.7547C>G · rs1359202442 · VCV2295897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.9486	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Overall
CADD	26.2	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 0.000169% European (non-Finnish) · 2/1,180,014 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,822 alleles · very rare exomes 2/1,461,548 · genomes 0/152,274 · joint denominator

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.Pro2516Arg
Coding: c.7547C>G
MANE Select: NM_002373
dbSNP: rs1359202442
Type: single nucleotide variant
Location: chr15:43529020 (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-pro2516arg (accessed [today's date]).

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