Is MAPK7 p.Asp364Glu (c.1092C>A) pathogenic?

MAPK7 p.Asp364Glu (c.1092C>A) is classified Uncertain significance in MAPK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: likely pathogenic (0.6259); Very rare (popmax 0.00223%, eas).

How common is MAPK7 p.Asp364Glu (c.1092C>A) in the general population?

MAPK7 p.Asp364Glu (c.1092C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MAPK7 p.Asp364Glu (c.1092C>A)?

AlphaMissense predicts likely pathogenic (score 0.6259) — an in-silico prediction, not a clinical call.

MAPK7 p.Asp364Glu

c.1092C>A · VCV4051618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6259	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -10.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.71, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,234 bp · p 6.6e-06 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,894 alleles

Overall 0.000124% 2/1,614,100 alleles · very rare exomes 2/1,461,726 · genomes 0/152,374 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Asp364Glu
Coding: c.1092C>A
MANE Select: NM_002749
Type: single nucleotide variant
Location: chr17:19381301 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 364: 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.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-asp364glu (accessed [today's date]).

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