Is MAP4 p.Ala2188Val (c.6563C>T) pathogenic?

MAP4 p.Ala2188Val (c.6563C>T) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: ambiguous (0.3856); Very rare (popmax 0.00167%, amr).

How common is MAP4 p.Ala2188Val (c.6563C>T) in the general population?

MAP4 p.Ala2188Val (c.6563C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MAP4 p.Ala2188Val (c.6563C>T)?

AlphaMissense predicts ambiguous (score 0.3856) — an in-silico prediction, not a clinical call.

MAP4 p.Ala2188Val

c.6563C>T · VCV3870293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.3856	ambiguous
REVEL	0.589	indeterminate
SaProt	LLR -8.97	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 23 kb · p 0.28 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1043V vs ClinVar A2188V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,022 alleles

Overall 6.2e-05% 1/1,614,084 alleles · very rare exomes 1/1,461,816 · genomes 0/152,268 · 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: MAP4
Protein: p.Ala2188Val
Coding: c.6563C>T
MANE Select: NM_001385682
Type: single nucleotide variant
Location: chr3:47857451 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03

Full MAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4 c.292+9T>G Benign ★★ same type
MAP4 p.Gln1950= Benign ★★ same type
MAP4 p.Leu516= Likely benign ★★ same type
MAP4 p.Val37= Benign ★★ same type
MAP4 p.Ala150Ser Uncertain significance ★ ⚠ same type
MAP4 p.Ala1922Val Uncertain significance ★ ⚠ same type
MAP4 p.Ala1926Pro Uncertain significance ★ ⚠ same type
MAP4 p.Ala1941Thr Uncertain significance ★ ⚠ 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/map4-p-ala2188val (accessed [today's date]).

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