Is MAPK7 p.Arg396His (c.1187G>A) pathogenic?

MAPK7 p.Arg396His (c.1187G>A) is classified Uncertain significance in MAPK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely benign (0.2971); Ultra-rare (popmax 0.0479%, nfe).

How common is MAPK7 p.Arg396His (c.1187G>A) in the general population?

MAPK7 p.Arg396His (c.1187G>A) is ultra-rare (popmax 0.0479%, nfe) (gnomAD).

What do computational predictors say about MAPK7 p.Arg396His (c.1187G>A)?

AlphaMissense predicts likely benign (score 0.2971) — an in-silico prediction, not a clinical call.

MAPK7 p.Arg396His

c.1187G>A · VCV3543163

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2971 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0479%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2971	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,234 bp · p 6.6e-06 · regional, not allelic
Overall
CADD	27.7	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 0.0479% European (non-Finnish) · 565/1,180,044 alleles

Filtering AF 0.0446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.0378% 610/1,614,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0479%	2,089
East Asian	0.0223%	4,489
Remaining individualsnot grpmax-eligible	0.0192%	5,209
African / African-American	0.0173%	5,774
Middle Eastern	0.0165%	6,062
Admixed American	0.00667%	14,995
South Asian	0.00329%	30,363
Finnishnot grpmax-eligible	0.00313%	31,984

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.Arg396His
Coding: c.1187G>A
MANE Select: NM_002749
Type: single nucleotide variant
Location: chr17:19381396 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 396: the 'necessary for oligomerization' region; a β-strand

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-arg396his (accessed [today's date]).

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