Is MAP1A p.Pro2076Ser (c.6226C>T) pathogenic?

MAP1A p.Pro2076Ser (c.6226C>T) is classified Uncertain significance in MAP1A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.1005); Very rare (popmax 0.00134%, afr); Associated with MAP1A-related disorder.

What condition is associated with MAP1A p.Pro2076Ser (c.6226C>T)?

MAP1A p.Pro2076Ser (c.6226C>T) is associated with MAP1A-related disorder (ClinVar).

How common is MAP1A p.Pro2076Ser (c.6226C>T) in the general population?

MAP1A p.Pro2076Ser (c.6226C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about MAP1A p.Pro2076Ser (c.6226C>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

MAP1A p.Pro2076Ser

c.6226C>T · rs773400796 · VCV3036453

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

MAP1A-related disorder

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.06	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 -0.54	GERP 0.62
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,720 alleles

Overall 6.2e-05% 1/1,613,088 alleles · very rare exomes 0/1,461,426 · genomes 1/151,662 · 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.Pro2076Ser
Coding: c.6226C>T
MANE Select: NM_002373
dbSNP: rs773400796
Type: single nucleotide variant
Location: chr15:43527699 (GRCh38)
Structure: AlphaFold pLDDT 94.44 · 41 PDB

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

Disease context

MAP1A-related disorder

Similar variants

MAP1A p.Pro2076Ala Uncertain significance ★ ⚠ same residue
MAP1A p.Arg2734Gln Uncertain significance ★★ same condition
MAP1A p.Lys2614Gln Uncertain significance ★ ⚠ same condition
MAP1A p.Trp2301Ter Uncertain significance ★ same condition
MAP1A p.Ala2201Val Uncertain significance ⚠ same condition
MAP1A p.Leu2057Arg Uncertain significance ⚠ same condition
MAP1A p.Arg2574His Likely benign same condition
MAP1A p.Asn1078Lys Likely benign same condition

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-pro2076ser (accessed [today's date]).

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