Is MAPK7 p.Ala296Thr (c.886G>A) pathogenic?

MAPK7 p.Ala296Thr (c.886G>A) is classified Pathogenic in MAPK7 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2025-01-01). AlphaMissense: likely benign (0.1234); Rare (popmax 0.704%, eas); Associated with scoliosis, isolated, susceptibility to, 1.

What condition is associated with MAPK7 p.Ala296Thr (c.886G>A)?

MAPK7 p.Ala296Thr (c.886G>A) is associated with scoliosis, isolated, susceptibility to, 1, type 2 diabetes mellitus (ClinVar).

How common is MAPK7 p.Ala296Thr (c.886G>A) in the general population?

MAPK7 p.Ala296Thr (c.886G>A) is rare (popmax 0.704%, eas) (gnomAD).

What do computational predictors say about MAPK7 p.Ala296Thr (c.886G>A)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

MAPK7 p.Ala296Thr

c.886G>A · rs147296805 · VCV427639

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.704%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

scoliosis, isolated, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign ⚠ discordant with ClinVar
REVEL	0.122	moderately benign-leaning
SaProt	LLR -7.09	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 12	GERP 0.5, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,234 bp · p 6.6e-06 · regional, not allelic
Overall
CADD	24.4	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 0.704% East Asian · 316/44,874 alleles

Filtering AF 0.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.615%

Overall 0.0222% 358/1,613,996 alleles · rare exomes 319/1,461,684 · genomes 39/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.704%	142
Remaining individualsnot grpmax-eligible	0.0384%	2,604
South Asian	0.011%	9,108
African / African-American	0.00799%	12,510
Admixed American	0.00167%	60,020
European (non-Finnish)	8.47e-05%	1,180,013

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.Ala296Thr
Coding: c.886G>A
MANE Select: NM_002749
dbSNP: rs147296805
Type: single nucleotide variant
Location: chr17:19381095 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 296: the protein kinase domain; the 'necessary for oligomerization' region; an α-helix

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

Disease context

scoliosis, isolated, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus

Similar variants

MAPK7 p.Pro587Leu Pathogenic ⚠ same condition
MAPK7 p.Pro648Leu Pathogenic ⚠ same condition
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-ala296thr (accessed [today's date]).

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