Is MAPK7 p.Arg797His (c.2390G>A) pathogenic?

MAPK7 p.Arg797His (c.2390G>A) is classified Uncertain significance in MAPK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-16). AlphaMissense: likely benign (0.1282); Very rare (popmax 0.00439%, sas).

How common is MAPK7 p.Arg797His (c.2390G>A) in the general population?

MAPK7 p.Arg797His (c.2390G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about MAPK7 p.Arg797His (c.2390G>A)?

AlphaMissense predicts likely benign (score 0.1282) — an in-silico prediction, not a clinical call.

MAPK7 p.Arg797His

c.2390G>A · rs541783142 · VCV2267579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1282 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1282	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 377 bp · p 0.002 · regional, not allelic
Overall
CADD	29.5	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,080 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00192% 31/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,770
East Asian	0.00223%	44,868
European (non-Finnish)	0.00212%	47,200
Admixed American	0.00167%	60,014

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.Arg797His
Coding: c.2390G>A
MANE Select: NM_002749
dbSNP: rs541783142
Type: single nucleotide variant
Location: chr17:19383170 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 797: 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.Arg797Cys Uncertain significance ★ ⚠ same residue
MAPK7 p.Arg797Ser Uncertain significance ★ ⚠ same residue
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

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-arg797his (accessed [today's date]).

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