Is MAPK7 p.Phe730Tyr (c.2189T>A) pathogenic?

MAPK7 p.Phe730Tyr (c.2189T>A) is classified Uncertain significance in MAPK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: ambiguous (0.5358); Very rare (popmax 0.00167%, amr).

How common is MAPK7 p.Phe730Tyr (c.2189T>A) in the general population?

MAPK7 p.Phe730Tyr (c.2189T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MAPK7 p.Phe730Tyr (c.2189T>A)?

AlphaMissense predicts ambiguous (score 0.5358) — an in-silico prediction, not a clinical call.

MAPK7 p.Phe730Tyr

c.2189T>A · rs1212849334 · VCV2293348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5358 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.5358	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -6.97	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 821 bp · p 0.1 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

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

Overall 0.000186% 3/1,614,186 alleles · very rare exomes 3/1,461,882 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,026
European (non-Finnish)	0.000169%	590,012

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: MAPK7
Protein: p.Phe730Tyr
Coding: c.2189T>A
MANE Select: NM_002749
dbSNP: rs1212849334
Type: single nucleotide variant
Location: chr17:19382838 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 730: the 'disordered' region; the 'may not be required for kinase activity; required to stimulate mef2c activity' region

Full MAPK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK7 p.Pro551Ser Benign/Likely benign ★★ same type
MAPK7 p.Ala288Ser Uncertain significance ★ ⚠ same type
MAPK7 p.Ala29Gly Uncertain significance ★ ⚠ same type
MAPK7 p.Ala334Thr Uncertain significance ★ ⚠ same type
MAPK7 p.Ala348Ser Uncertain significance ★ ⚠ same type
MAPK7 p.Ala360Val Uncertain significance ★ ⚠ same type
MAPK7 p.Ala481Ser Uncertain significance ★ ⚠ same type
MAPK7 p.Ala497Val 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/mapk7-p-phe730tyr (accessed [today's date]).

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