Is MAPK7 p.Arg369His (c.1106G>A) pathogenic?

MAPK7 p.Arg369His (c.1106G>A) is classified Uncertain significance in MAPK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1754); Ultra-rare (popmax 0.0211%, nfe).

How common is MAPK7 p.Arg369His (c.1106G>A) in the general population?

MAPK7 p.Arg369His (c.1106G>A) is ultra-rare (popmax 0.0211%, nfe) (gnomAD).

What do computational predictors say about MAPK7 p.Arg369His (c.1106G>A)?

AlphaMissense predicts likely benign (score 0.1754) — an in-silico prediction, not a clinical call.

MAPK7 p.Arg369His

c.1106G>A · rs371955456 · VCV2524975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1754 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1754	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP -0.55, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,234 bp · p 6.6e-06 · regional, not allelic
Overall
CADD	24.7	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 0.0211% European (non-Finnish) · 249/1,180,040 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0181%

Overall 0.0167% 270/1,614,060 alleles · ultra-rare exomes 256/1,461,732 · genomes 14/152,328 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0211%	4,739
Admixed American	0.0117%	8,575
African / African-American	0.00933%	10,722
Remaining individualsnot grpmax-eligible	0.008%	12,502
Finnishnot grpmax-eligible	0.00157%	63,878
South Asian	0.0011%	91,086

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.Arg369His
Coding: c.1106G>A
MANE Select: NM_002749
dbSNP: rs371955456
Type: single nucleotide variant
Location: chr17:19381315 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 369: the 'necessary for oligomerization' region; an α-helix

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

Similar variants

MAPK7 p.Arg369Cys 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
MAPK7 p.Ala481Ser 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-arg369his (accessed [today's date]).

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