Is MAPK7 p.Ala497Val (c.1490C>T) pathogenic?

MAPK7 p.Ala497Val (c.1490C>T) is classified Uncertain significance in MAPK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.0704%, amr).

How common is MAPK7 p.Ala497Val (c.1490C>T) in the general population?

MAPK7 p.Ala497Val (c.1490C>T) is ultra-rare (popmax 0.0704%, amr) (gnomAD).

What do computational predictors say about MAPK7 p.Ala497Val (c.1490C>T)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

MAPK7 p.Ala497Val

c.1490C>T · rs192160574 · VCV2246244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0704%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.18	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 0.39	GERP -0.91, phastCons 0.86
Regional constraint	o/e 0.80	unconstrained · MANE · 1,234 bp · p 6.6e-06 · regional, not allelic
Overall
CADD	13.58	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 0.0704% Admixed American · 35/49,698 alleles

Filtering AF 0.052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0457%

Overall 0.0341% 527/1,546,460 alleles · ultra-rare exomes 480/1,394,140 · genomes 47/152,320 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0704%	1,420
European (non-Finnish)	0.04%	2,499
Remaining individualsnot grpmax-eligible	0.0388%	2,580
Ashkenazi Jewishnot grpmax-eligible	0.00809%	12,354
African / African-American	0.0055%	18,183
Finnishnot grpmax-eligible	0.0033%	30,289
South Asian	0.00127%	78,912

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.Ala497Val
Coding: c.1490C>T
MANE Select: NM_002749
dbSNP: rs192160574
Type: single nucleotide variant
Location: chr17:19381793 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 497: the 'disordered' region; 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.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.Ala501Val 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-ala497val (accessed [today's date]).

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